|Year : 2012 | Volume
| Issue : 1 | Page : 25-40
ICAAICON 2011 - Abstracts of papers presented (not peer reviewed)
|Date of Web Publication||10-Dec-2012|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. ICAAICON 2011 - Abstracts of papers presented (not peer reviewed). Indian J Allergy Asthma Immunol 2012;26:25-40
Biotic aeroallergens and human health
Prof. S. T. Tilak and Dr. S. B. Jogdand.
18, Vidyasagar Society, Nr. Mahesh Society, Bibwewad, Pune
The paper reviews the work carried out at Aurangabad and subsequently continued in Pune, Both outdoor and indoor allergens have been investigated in varied environments and their relevance in causing hazardous effects on human health. Allergy clinic, Government Medical College at Aurangabad under Prof. Talib provided useful support while support in Pune was extended by BharaþiVidyapeeth.
Role of environment and meteorological parameters on the load of airborne allergens provided basic information. A Her genie forms were specially studied along with their seasonal variation and impact on Patients. Indoor allergens are now posing a great challenge due to several reasons among which increase in moisture content in an indoor environment supported by cooling systems has added new dimensions to sick building syndrome. Due to rapid growth in metropolitan areas with more air-conditioning in buildings new challenge of sick buildings is now a cause of major concern of tomorrow.
In an attempt to survey the aeroallergens of garbage Depot at l ^ othrud, Pune and it's relevance to surrounding population in enhancing allergic diseases, the results showed many interesting observations. The High court at Bombay in writ Petition accepted the scientific findings and ordered the Pune Corporation to shift garbage Depot. Accordingly the depot is shifted,
Allergic disorders, the truth unveiled
Dr. Syed Arham Husain, Dr. M. A. Khan, Bhopal
Objective: Allergen exposure is of utmost importance during pregnancy, infancy and childhood and the avoidance of exposure is leading to pandemic of allergic disorders throughout the world.
Methodology: Observations were made after through study amongst,
Results: In this multicentric study it was observed that the incidence of allergy amongst population related agriculture and farmlands to be 2%, amongst people from small city to be around 4 % (1995-96), all the infants and children getting exposure to farmlands never showed signs of allergy, amongst children born to USA migrants who were born and brought up at USA most of them developed allergy symptoms.
- Population living in agricultural farm lands,
- Population from small city,
- 30 infants and children from small city visiting the village farmlands during last 18 years,
- Study of allergy in people migrating to USA for employment and their children born and brought up at USA.
- Comparative study of incidence of allergy from available resources world wide.
Conclusion: Exposure to allergens is the rule, and avoidance is a disaster for future generations.
Immuno therapy in bronchial asthma - myths and facts
Prof. (Dr.) KV Ramana Rao
Prof. and HOD (TB and Chest), GSL Medical College, Rajahmundry-533296, A.P., India
Bronchial Asthma is still a perplexing disease. Known since 460 B.C.
Recurrent expiratory dyspnoea of varying intensity occur, not due to infection/infestation/organic lesion. Heredity, atopy, bronchial Hyperreactivity, Hormones, Immuno-deficiency, Adeno cyclase deficiency, Climatic factors predispose. Attacks precipitated by Aero Allergens, Infection, Emotion, Exercise, Drugs, Nasal Polyps etc.
Aero Allergens are difficult to manage effectively.
Immuno Therapy is one treatment modality advocated. Overall outcome not cost effective. Mostly given for Aero Allergens. Different studies give no conclusive evidence in this regard.
Extracts of different Aero Allergens are given Intra dermally and the reaction to same is recorded (Type-I Immunological reaction). In multiple positives skin test reactions, immuno therapy may not be effective, since correct titration of the antigen dose is not possible. Not very beneficial when there are multiple positive skin test reactions.
The Aero Allergens and their concentration vary from season to season. So, multiple allergens may have to be used for Immuno Therapy. Efforts are on for preparation of more absolute and pure extracts/refine the allergens by Genetic engineering/synthetic peptide Chemistry/develop allergen derived T-cell peptide epitopes. Further treatment modalities are being studied.
Fine gold, et. al opine (2002) that immunotherapy is not an all/none therapy. More effective in allergic Rhinitis/Hay fever/Childhood Asthma. Critically review with environmental control and drug therapy vs. immuno therapy.
Abramson et. al. 2010 report diminution of symptoms/drug dose and increase in Bronchial Hyper reactivity.
Immunomodulating Effect of Dioscorea Bulbifera and Fosinopril in Patient of Diabetic Nephropathy
Prof. Dr. R. G. Singh, U. Singh, A. Tiwari, S. Singh
Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, U.P., India
Objective: In this comparative evaluation of antiproteinuric effect of Fosinopril and a herbal drug, Discoriea bulbifera has been undertaken in overt proteinuric patients. As most of the diabetic patients are diagnosed when overt proteinuria has developed and antiproteinuric effect of Fosinopril has not been studied in our situation.
Methodology: Inclusion Criteria: Patient of both sexes from pediatric to adult, diabetic patient with evidence of nephropathy.
Exclusion Criteria: Patient already taking ACE/ARB, History of allergy to any kind of trial drugs, severely ill patient with advanced renal failure, Acute on CKD, Hypertension requiring multiple drugs, Patients with bilateral renal artery stenosis.
Termination Criteria: Rapid decline in renal function requiring RRT, Death of the patients due to any causes, acute on CRF, Patient completing 6 months follow up as a first phase patient. The patients were divided in three groups.
Group A: Patient who received Fosinopril in a dose of 5 to 40 mg/day.
Group B: Patient who received capsule Dioscorea bulbifera in a dose of 500mg BD.
Group C: Patient who received placebo 500mg BD.
The patient after detailed interrogation and examination were subjected to hematological, Biochemical Analysis, Urinalysis, ECG, Radiological Examination and Immunological examination which was repeated every monthly till six months.
Results: The males dominated over the females patient with a male to female ratio of 2.6:1. In patients treated with Dioscorea bulbifera anorexia, vomiting oedema and weakness improved in 31%, 30%, 40% and 42% respectively. There was no clinical deterioration of patient. The patient treated with Fosinopril, Dioscorea bulbifera and placebo there was change in 24 hours urinary protein excretion from 2.44 ± 1.46 to 2.29 gm/day in group A, 2.71 ± 1.56 to 2.55 ± 1.45 gm/day in group B and 2.09 ± 0.99 to 2.22 gm/day in group C. There was decrease in proteinuria at the end of study in group A, 5.16% in group B compared to placebo group which shows statistically significant. In patient treated with Dioscorea bulbifera, there was significant reduction in cholesterol, triglyceride and LDL by 11.8%, 5% and 18.1% respectively at the end of follow up period. This suggests hypolipidemic action of Dioscorea bulbifera. In patient treated with Fosinopril and Discorea bulbifera, TGT-B, level decreased from 53.43 ± 35.54 to 38.26 ± 24.37 mg/dl in group A, 52.84 ± 9.25 to 36.62 ± 7.32 mg/dl in group B which was statistically significant (P < 0.001). The IL-6 and TNF-a was found much less in the drug treated groups more in the herbal drug.
Conclusion: All the patients were followed up for a period of 6 months showed no significant decline in renal function and good control of lipid level, glycemia and blood pressure in Fosinopril and Discorea bulbifera. Hence the trial drug seems to be effective in retardation of progression of diabetic nephropathy with adequate immunomodulatary effect.
Assessment for Efficacy of Breathing Exercises Over Improvement in Health Impairment Due to Asthma using St George's Respiratory Questionnaire
Dr. Dipti Agrawal, Prof. S. Sood, Prof. P. P. Gupta
Assistant Professor, PGIMS, Pt. B D Sharma University of Health Sciences, Rohtak, Haryana, India
Background: Breathing exercises have often been described to be useful in asthma management.
Objective: To assess the efficacy of breathing exercises [Pranayamas] in improving health impairment due to asthma using St George's Respiratory Questionnaire (SGRQ).
Methods: 60 stable asthma patients [34 females] receiving optimal treatment for 3 months or more as per GINA guidelines were included. They performed seven breathing exercises (BEx) [Pranayamas] under supervision at Yoga centre at our Institute for 3 months in addition to their regular medications. SGRQ (one month symptoms version) was used to assess symptom, activity, impact components, and total scores to assess the efficacy.
Results: Their mean age was 25.45 ± 5.41 years, mean FEV1 was 2.492 ± 0.358 L, and mean PEFR was 283.82 ± 51.12 L/min. The various parameters of SGRQ are shown in (Table 1):
Decrease in symptoms, activity and total SGRQ scores each was significantly correlated with FEV1, FEV1/FVC ratio and PEFR; decrease in impact score was significantly related only with FEV1/FVC ratio.
Conclusions: Breathing exercises significantly decreased all components scores of SGRQ signifying a global improvement in health impairment due to asthma; this improvement was in addition to that achieved with optimal asthma therapy alone.
Dermatoglyphics in Bronchial Asthma
Dr. Mahendra Wawhal. Dr. S. H. Talib
MGM's Medical College, Aurangabad, India
Aims and Objectives: To study if a correlation exists between bronchial a sthma and dermatoglyphic features.
To explore if Dermatoglyphics can help to detect the possibility of bronchial asthma in persons who are presently non-asthmatic, including the predictive possibilities of bronchial asthma in the asymptomatic children of asthmatic parents i.e., asthmatic mother/father
Method: Total 40 patients of bronchial asthma were studied reporting in the OPD and IPD at Government Medical College and Hospital, Aurangabad from December 2002 to December 2003. Also, 15 asymptomatic children of asthmatic parents were included. A group of 40 healthy individuals served as Control Group. After detailed history, physical examination and investigations, black thumb imprint ink applied impressions of both palms were recorded to study and have a systematic observation and tabulation of various features of palm in asthmatic patients, asymptomatic children of asthmatic parents and the control group.
Result: The Dermatoglyphic features viz. the loops, arches and whorls in the palms of adult asthmatic patients were studied and compared with the control group and it was found that the asthmatic subject group had predominance of thumb whorls (65%) as compared to 41.25 % occurrence in controlled group. Also, it was found that the occurrence of thumb whorls predominates (66.67%) in occurrence in asymptomatic children of asthmatic parents. These both results were found to be statistically significant. There was no statistical significance regarding the occurrence of loops and arches.
Conclusion: The observation of dermatoglyphic features in the palms of the patients of bronchial asthma, normal subjects and asymptomatic of asthmatic patients were analyzed and it was concluded that occurrence of thumb whorls was significantly higher in the adult asthmatic group (65%) as well as in the asymptomatic children of asthmatic parents group (66.67%) as compared to the controlled group(41.25%). This feature i.e. the occurrence of thumb whorls may be employed as a dermatoglyphic diagnostic criterion for bronchial asthma.
The asymptomatic children of asthmatic parents group demonstrated a significant similarity of ermatoglyphic patterns in terms of thumb whorls with their asthmatic parents. This may serve as a tool to predict the possibility of bronchial asthma in future.
Allergen Specific Immunotherapy in Allergic Conjunctivitis due to Dust Mite
Dr. Sanjay Pawar, Dr. Sunanda Pawar, Ms. Hayatbi Pathan, Ms. Usha Lokare
Shriratna Hospital. Karad (Maharahtra), India
Background: The safety and the efficacy of allergen specific Immunotherapy by subcutaneous route in perennial conjunctivitis caused by house dust mite were evaluated in 89 patients for 24 months.
Methods: Group of 89 patients diagnosed by ophthalmologist included in study. Patients of allergic conjunctivitis included in this study underwent Skin allergy test and specific IgE tests for dust mite allergens. Out of 89 patients 43 received Allergen specific Immunotherapy (SIT) subcutaneous injections with standardized Dermatophgoides farinae (D. f.) and Dermatophagoides pteronyssinus (D.pt.) allergen extract. While 46 patients are only treated by conventional treatment by using local steroids and antihistaminic drops. The vaccine was supplied by a commercial company as per the prescription for each patient. The subjects generally received three concentrations of antigens ending with the most concentrated solution. These solutions were: 1:5000 (w/v), 1:1000,1:500 and 1:50. Later on maintenance immunotherapy was continued with the 1:50 concentration for 24 months. Results were evaluated on 2,6,12,18 and 24 months by using Total Symptom Score(TSS), Local Medication use, Clinical examination grading, Quality of Life evaluation(QOL).
Results: Of the 89 patients included, only 81 completed the study (43 in the Immunotherapy group and 46 in the Non Immunotherapy group,). Three out of 43 (6.9%) patients dropped out because of insufficient efficacy in the Immunotherapy group compared to five out of 46 (10.8%) in the non immunotherapy group. Sum of all four Primary end point criteria's are scored against five group of efficacy evalution. No improvement 8 (9.8%), marginal improvement 16(19.7%),improvement 23 (28.3%) and significant improvement 35(43.2%). In group of 35 improved patients 26 (74.2%)were received immunotherapy while 9 (25.7%)patient did not.
Conclusion: Two years treatment with Subcutaneous house dust mite immunotherapy significantly reduced symptoms and medication use in allergic conjunctivitis patients. This was associated with a greater subjective improvement and quality of life in patients of perennial conjunctivitis caused by house dust mites.
Chronic Urticaria with Reference to Etiology and Investigations
Dr. Mohd. Tariq Iqbal, Dr. M. Y. Khedkar, Dr. A. Sonarikar, Dr. A. Deshmukh, Dr. V. Desarda, Dr. A. Gulanikar
Aim: to evaluate types of chronic urticaria with reference to etiology and investigations.
Background: chronic urticaria has different types of clinical presentations causes. The study was started to find out the types of chronic urticaria.
Methods: the study group consisted of 102 patients of chronic urticaria of more than 6 weeks duration. Various types of tests and investigations done in all the patients.
Results: chronic idiopathic urticaria 52.94%, cold urticaria 9.80%, cholinergic urticaria 6.01%, dermographism 19.60%, pressure urticaria 1.96%, solar urticaria 1.96%, drug induced urticaria 3.92%, inhalants induced 00 . 98%, food induced 13.72%, infestation induced 1.96%, bacterial foci 4.90%, aquagenic 1.96%, heat induced 00%.
Conclusion : chronic idiopathic urticaria is the most common type of chronic urticaria in our study. Dermographism is the second most common type and food inuced urticariais the third most common type in our study.
Sensitization to Fungal Antigens in 1440 Patients of Jalandhar and Neighbouring Area in Punjab
Dr. V. P. Jerath
Material and Methods: The data of positive reaction to fungi on 1500 patients of nasobronchial allergy has been included in this study. Allergy test (skin testing with intradermal injection of antigen) was conducted on patients and the results were interpreted by comparing the wheal produced by the test substance in relation to the control.
Results: While analyzing the results 60 patients were excluded because of (±) or one plus (+) cutaneous reaction to fungal antigens. Topping the list, cladosporium was positive in 158 patients (11%) followed by Alternaria tenuis in 144(10%), Curvularia lunata in 108(75%), Helminthosporium sp. in 115(8%).Moderate positive were Rhizopus nigricans in 92 (6.4%) patients, Candida albicans in 86(6%), Asperillus fumigatus in 86(6%), Mucor mucedo in 83(508%), Aspergillus niger in 81 (5.6%), Phoma batae 79 patients (5.5%), Aspergillus tamarii 72 (5.5%), Trichoderma 72 (5%). The low positive were penicillium in patients(3.5%), Aspergillus flavus 43(3%), Nigerospora 41 (2.5%), Neurospora sitophila 41 (2.5%), Epicoccum purpurascens 31 (22%), Aspergillus versicolor 30 (2%) and Fusarium solani 28 (2%) patients.
Indoor Aeroallergens of Dwellings
Dr. B. N. Pande
Emeritus Professor, MGM'S Institute of Biosciences and Technology, MGM Campus, N-6 CIDCO, Aurangabad-431003, (M.S.) India
The word "allergy" means an altered reactivity of the body to harmless environmental substances. In other words, in allergic individuals the body starts producing increasing amounts of an antibody, called immunoglobulin E (IgE) in response to exposure to common harmless environmental substances that it recognizes as "Allergens" (antigens). The interaction between IgE and the allergens results in the manifestation of symptoms.
An ambient air in intramural and extramural environment is charged with inorganic as well as organic particles, the latter includes pollen, fungal spores, hyphal fragments etc. The major sources for the contamination of intra and extramural ambient air are infected plants, their parts, excreta of different animals, saprophytically growing micro-organisms on decaying or dry plant parts, mills bakeries, aerosols generated from coughing and sneezing of diseased persons, dust particles etc. Maun sell (1954), Pande (1994), Tilak and Pande (1997) studied the concentration of airborne spores in dwellings under normal conditions and under repair. They observed the high concentration of fungal spores in dwellings where repairing activities were going on.
In view of the above, in the present investigation also an attempt has been made to assess the occurrence of fungal spores, pollen grains, hyphal fragments prevailing in the air inside the dwellings at different places, their relevance to human allergy, their seasonal variation and their correlation with meteorological parameters.
Airborne fungal morphotypes were trapped using Tilak Air Sampler from 1 st January to 31 st December 2007 in an indoor atmosphere of dwellings. Total 54 fungal spore types and 7 Other types were recorded. The group Deuteromycotina contributed maximum 72.18%, followed by Ascomycotina 14.27%, other types 6.60%, Zygomycotina 3.70% and Basidiomycotina 3.24% The major fungal morphotypes, already recorded as allergenic such as Cladosporium contributed maximum to the tune of 28.34%,followed by Alternaria 9.25%, Periconia 4.98% Nigrospora 3.83%, Curvularia 3.71 %, Helminthosporium 2.92%, Leptosphaeria 2.65% etc.
A long term study of indoor atmospheric surveys in the dwellings is absolutely necessary in orfder to understand the clear picture of microbial spectrum and for their effective control.
Keywords: Allergens, Dwellings, Tilak Sampler, Immunoglobulin (IgE).
Clinical Profile of Nevirapine Induced Skin Rash in HIV-AIDS Patients on ART
Dr. Mangala Sonavani (Borkar), Dr. Pankaj Golegaonkar, Dr. Manohar Kamble, Dr. Shilpa Pawar
Retrospective analysis of HIV-AIDS patients who were initiated on Anti Retroviral Therapy on Nevirapine based regimen over a period of 4 years (between June 2007 to September 2011) was done at ART center Govt. Medical College, Aurangabad, India
105 Peanut oral immunotherapy and omalizumab treatment for peanut allergy
- A total of 3630 patients were initiated on Nevirapine based regimen, out of whom 226 (6.22%) developed Nevirapine induced rash. Out of 226,224 were adults and 2 were pediatric patient. (<14 years)
- 183 (80.97 %) patients were between 20 to 40 years of age. Out of 226,159(70.35%) were females and 67 patients (29.65%) were males.
- Out of 226, in 184 (81.41%) patients, the baseline CD4 was less than 250 whereas 42(18.59 %) patients had a baseline CD4 count more than 250. Out of 226, 69 (30.53%) patients developed rash within 15 days of onset of ART, while 157 (69.47%) developed rash after 15 days to 60 days of treatment with Nevirapine.
- Out of 226 (56.19 %), 127 patients develop mild rash, while 92 (40.7 %) patients had moderate and only 7 (3.09 %) patients had severe grade of rash i.e. Steven-Johnson syndrome.
- All the patients recovered from the rash. There were no deaths.
- Out of 226, 223 were 'treated by withdrawing Nevirapine and supportive therapy i.e. anti histaminics with steroids. 3 patients improved on their own.
- Rash due to Nevirapine is a relatively common adverse effect but the prognosis is good if detected early and Nevirapine is discontinued.
- In this study this adverse effect was observed in 81.4 % cases with low CD4 count (<250) (as against the genero 1 observation that it is found in cases with hiaher CD4 count)
M. Henson, A. Edie, P. Steele, J. Kamilaris, M. Kulis, A. Thyagarajan, B. P. Vickery, A.W. Burks
Duke University School of Medicine, Durham, NC
Rationale: We hypothesize that treatment with omalizumab prior to starting oral immunotherapy (OIT) will reduce symptoms, allowing acceleration of the build-up phase and achievement of maintenance dosing more quickly.
Methods: Peanut-allergic patients aged 12 years and older were enrolled in this study. Omalizumab was given for 4 months prior to initiation of OIT, followed by a modified rush day(s), a build-up period, and a daily home maintenance phase with a final dose of 4000 mg of peanut protein. Omalizumab was continued for 1 month after reaching maintenance dosing.
Results: Six patients had evaluable safety data. The median peanut-specific IgE level in this group was 68.7 kU/L. The median total IgE level was 486.5 kU/L. 6/6 patients experienced symptoms on the rush desensitization days with 20/21 symptoms graded as mild, primarily respiratory in nature, comparable to previously published safety data for rush desensitization without omalizumab. The median peanut starting dose after rush desensitization with omalizumab was 300 mg (range: 100-400), higher than that seen without omalizumab pretreatment. On dose escalation days, 9.5% of doses (6 of 63) resulted in symptoms in the omalizumab group, in contrast to 43.3% of doses (123 of 284) resulting in symptoms in previous studies [RR 0.22 (95% CI 0.10-0.48), P<0.0001].
Conclusion: These results, although limited by small sample sizes, suggest that omalizumab therapy has the potential to reduce side effects during dose escalation and allow a higher starting dose of peanut. This may enhance safety and allow patients to reach maintenance dosing sooner than in previous peanut OIT trials.
278 Oral corticosteroid use increases the risk of glucocorticoid-related adverse events in asthmatics
J. L. Zazzali 1 , M. Broder 2 , E. Chang 2
1 Genentech, Inc., South San Francisco, CA, 2 Partnership for Health Analytic Research, Beverly Hills, CA
Rationale: Oral corticosteroids (OCS) are a mainstay of asthma therapy for managing severe symptoms and exacerbations. Prolonged systemic exposure to glucocorticoids is known to be associated with increased risk of glucocorticoid-related adverse events (GAEs). Our objective was to determine the risk of GAEs associated with cumulative OCS exposure in asthmatics.
Methods: Retrospective cohort analysis of adult asthmatics using a HIPAA compliant claims database. Patients were continuously enrolled during 2002-2003 and were followed up until the end of enrollment or study end (2007) whichever was earlier. Patients with potential GAEs in the first year were excluded. Cox regression models estimated adjusted hazard ratios of the risk of GAEs (osteoporosis, fracture, and cataracts) for different OCS exposure levels, measured by cumulative prednisone-equivalent dose as recorded on pharmacy claims, while adjusting for age, gender, region, usual care physician specialty, and chronic conditions.
Results: We examined 37,891 asthmatics (mean age: 44.9 years; 65.7% female). For every 1000 mg increase in prednisone-equivalent OCS exposure, the risk of a claim for osteoporosis was 3% higher, the risk of a claim for fracture was 2% higher, and the risk of a claim for cataracts was 2% higher.
Conclusions: In asthmatics, greater cumulative OCS exposure is associated with statistically significant increased risks of osteoporosis, fracture, and cataracts.
352 Identification of increased oral eosinophils in patients with eosinophilic esophagitis using oral rinse analysis: Proof of concept
McMaster University, Hamilton, ON, Canada
Rationale: Patients with suspected eosinophilic esophagitis (EE) require an endoscopic biopsy for confirmation. Evaluations of oral rinses from EE patients were assessed for increased eosinophils (Eos) as a possible screening tool.
Methods: EE patients were asked to rinse with 10 ml of saline for 30 seconds. Expectorates were fixed with formaldehyde. Following filtration to remove epithelial cells, samples were centrifuged at 3000 rpm. Cell pellets were re-suspended in PBS. Fifty (50) microliters of cells were stained with Hematoxylin and Eosin. Eos and neutrophils (PMN) were visualized and quantified under light microscopy by characteristic nuclei, eosin containing granules and size. Quantification of Eos was assessed in microscopic fields. Control samples were obtained.
Results: Six patients with biopsy-proven EE showed an average of 19% Eos (range: 10-12%) of all cells evaluated. This was significantly more than control, (mean: 3.1%; range: 2-4%). There was a higher absolute number of PMN's in control patients as compared to patients with EE (111 vs. 49).
Conclusions: There is evidence of increased amount of Eos isolated from oral rinses of EE patients. A combination of increased Eos and decreased PMN's resulted in an increased relative proportion of Eos in patients with EE. The analysis of oral rinses may serve as a screening tool for patients suspected of having EE.
102 A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy
S. D. Narisety 1 , C. Keet 1 , P. Guerrerio 1 , J. Schroeder 2 , R. Hamilton 2 , R. A. Wood 1
1 Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, 2 Department of Medicine, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, MD.
Rationale: To compare safety and efficacy of oral versus sublingual immunotherapy (OIT and SLIT) for the treatment of peanut allergy.
Methods: After a baseline double-blind placebo-controlled food challenge (DBPCFC, maximum 1 g peanut protein), subjects were randomized to active SLIT/placebo OIT or active OIT/placebo SLIT. After initial escalation, SLIT/OIT doses were increased biweekly/weekly to 3696 mg/day SLIT and 2000 mg/day OIT. A 10 gm DBPCFC was completed after 6 months of maintenance.
Results: A total of 21 subjects, 7-13 years (median 11.1; male 52%), were enrolled. Baseline characteristics included median total IgE 667 kUA/L (range: 170-1557), peanut IgE 169 kUA/L (range: 35.1-814), peanut IgG4 1.12 mgA/L (range: 0.19-5.89), 5-log peanut endpoint skin titration (PEST) mean wheal 5.5 mm (range: 1.3-8.9), and DBPCFC threshold 21 mg (range: 1-146). Three subjects withdrew (1 systemic reaction, 1 GI symptom, 1 unrelated to study). There were significant increases at maintenance in total IgE (median: 844; range: 201-3938; P<0.001), peanut IgE (median: 344; range: 47.4-1960; P<0.001), and peanut IgG4 (median: 5.79; range: 0.47-47.2; P<0.001). Of the 9 subjects completing the 6 month DBPCFC, the median challenge threshold increased to 246 mg (21-4996; P<0.05) and PEST mean wheal decreased to 1.8 mm (range: 0.7-7.2; P<0.05). Significant increases in total and peanut IgE remained (P<0.05). Symptoms elicited by the 4772 home doses included: 15.4% oropharyngeal, 10.2% GI, 3.8% lower respiratory, 2.4% skin, and 0.9% upper respiratory. Treatment included antihistamines (43.2% of doses), beta2-agonists (1.3%), and epinephrine (1 dose).
Conclusions: Preliminary results demonstrate peanut SLIT and OIT are effective in changing challenge threshold, serologic markers, and skin.
95 Oral immunotherapy for egg allergy clinical and immunologic results
G. B. Pajno, L. Caminiti, D. Vita, G. Crisafulli
University of Messina, Messina, Italy
Rationale: Allergy to hen's egg represents an important issue in medical practice. The majority of children with IgE-mediated food allergy can achieve spontaneous tolerance to egg. However, some children have persistent symptoms beyond the age of 5; for these children we performed oral immunotherapy (OIT) with egg.
Methods: Twenty-eight children aged 5 to 16 years were equally randomized to desensitization with egg white (EW) or placebo. We used dried capsules containing EW (ovalbumin, ovomucoid, ovotransferrin) and talcum powder as excipient. The placebo's capsules containing only talcum powder (Lofarma, Milan, Italy). Specific IgE, and Ig4 levels to EW were measured at baseline and at the end of the study. Double-blind placebo-controlled food challenge (DBPCFC) was carried out at the beginning and at the end of the trial.
Results: Full tolerance to egg (200 mg) was achieved in 12 active patients (86%). One patient stopped desensitization after experiencing urticaria, rhinitis, and wheezing. One patient achieved partial tolerance, tolerating the dose of 50 mg egg. No reactions occurred in controls, whose sensitivity to EW remained unchanged. Specific IgG4 level increased (median EW IgG4 level) from 1.80 mg/mL at baseline to 24.18 mg/mL, P <.002. Only a slight decrease of both EW and ovomucoid-specific IgE was observed (median EW IgE level decreased from 24.32 kU/L at baseline to 18.12 kU/L, P<.06). No significant changes occurred in the placebo group.
Conclusion: This updosing desensitization for egg IgE-mediated food allergy performed under medical supervision was effective, rather safe and induced immunologic changes.
89 The prevalence of clinical cross-reactivity of non-peanut legumes to peanut in patients with persistent peanut allergy
D. L. Neuman-Sunshine 1 , J. A. Eckman 2 , C. A. Keet 3 , E. C. Matsui 3 , R. D. Peng 4 , P. J. Lenehan 3 , R. A. Wood 3
1 The Johns Hopkins University School of Medicine, Department of Medicine, Division of Allergy and Immunology, Baltimore, 2 University of Cincinnati, Department of Internal Medicine, Division of Immunology, Cincinnati, OH, 3 The Johns Hopkins University School of Medicine, Department of Pediatrics, Division of Allergy and Immunology, Baltimore, 4 The Johns Hopkins Bloomberg School of Public Health, Baltimore
Rationale: To describe the prevalence of non-peanut legume (NPL) allergy in patients with persistent peanut allergy.
Methods: Records of peanut allergic patients seen in a referral clinic were reviewed. Patients with a clear reaction history and positive skin test or IgE to a NPL were included.
Results: Of 793 patients (median age at initial observation: 1.4 years; range: 0-16) with persistent peanut allergy, 75 (9.5%) were considered NPL allergic (median age at diagnosis: 1 year; range: 0.1-15.6), including soy 48, pea 19, lentil 7, chickpea 4, green bean 3; 69 reacted to 1 NPL, 5 to 2, 1 to 3. A total of 106 NPL reactions were reported: soy 69, pea 21, lentil 7, chickpea 5, green bean 3, with symptoms including urticaria/angioedema, 40.6%, gastrointestinal, 30.2%, atopic dermatitis (AD), 23.6%, oral erythema/pruritus, 13.2%, lower respiratory, 6.6%, cardiovascular, 1.9%. 82.7% had AD, 64% asthma, and 62.7% allergic rhinitis. AD was more common in NPL allergic than peanut-only allergic patients (82.7% versus 69.1%, P<0.02). Median peak NPL-IgE values were: soy 30 kU/L, lentil 15.4, chickpea 21.9, pea 15.6, green bean 9.3. Median peanut-IgEs values were greater in NPL allergic patients (initial 69.7 kU/L versus 25.8, P <0.002; peak >100 versus 59.5, P<0.002). Median peak NPL-IgE to peanut-IgE ratios were: soy 0.6, lentil 1, chickpea 2, pea 0.6, and green bean 1.9.
Conclusions: In this referral population, the clinical cross-reactivity of NPL to peanut was 9.5%. In NPL allergic patients, the median peak NPL-IgE to peanut-IgE ratio was consistently >0.5. NPL allergic patients were also more likely to have AD and higher peanut-IgE levels.
173 Absence of IgE neosensitization in house dust mite allergic patients following sublingual immunotherapy
P. Moingeon; Stallergenes SA
Rationale: The impact of sublingual immunotherapy (SLIT) on allergen-specific IgE and IgG responses, as well as the risk of neosensitization, remains to be evaluated in large cohorts of patients.
Methods: Antibody responses were assessed in sera from 509 European HDM-allergic patients before and after 1 year of daily sublingual immunotherapy, using tablets containing either Dermatophagoides pteronyssinus plus D. farinae extracts or placebo with an additional year of follow-up after treatment. IgE and IgG4 antibodies specific for group 1, 2 and 10 allergens were assessed using Immuno Solid-Phase Allergen Chip (ISAC).
Results: After 1 year of SLIT, both mite-specific IgE and IgG4 titers increased by 1.5- to 4-fold in the active group, but not in the placebo group. IgG4 induction occurred in a subgroup of ''immunoreactive'' patients, without any correlation with improvement in the rhinoconjunctivitis symptom score. Pre-existing IgE levels to mite allergens were usually boosted during immunotherapy, but no de novo IgE responses were induced during SLIT in patients who were not sensitized prior to immunotherapy. Similarly, no neosensitization to wheat germ or yeast components used in the mite culture medium was observed, consistent with the lack of detection of these proteins in mite extracts.
Conclusions: We document on a large cohort of patients over a 2 year period that the induction of seric mite-specific IgG4 is not a biomarker for SLIT clinical efficacy. SLIT does not induce IgE neosensitization to allergens contained in the vaccine, including groups 1, 2 as well as the food-related group 10 allergens.
179 Grass Pollen immunotherapy in children: Safety aspects
M. I. Garcimartin, M. Vazquez de la Torre Gaspar, F. Ruano Perez, N. Blanca Lopez, E. Seoane Reula, M. De Diego, M. Canto Diez
Hospital Infanta Leonor, Madrid, Madrid, Spain
Rationale: Cluster schedules are an accelerated procedure to achieve maintenance dose and allow the administration of high allergen doses in a short time interval. We investigate the safety profile of cluster schedule with grass pollen cluster subcutaneous immunotherapy (SCIT), in children with allergic rhinitis and/or asthma.
Methods: A total of 131 patients, aged 5 to 14 years (51 females and 80 males) with allergic rhinitis and/or asthma due to grass pollen, were included in an open-label prospective trial in a 3 year period (from 2008 to 2011). Grass pollen allergy was confirmed by clinical history, skin prick test, and serum-specific IgE. Patients received grass pollen SCIT, in a cluster schedule; up-dosing consisted of six injections over 3 weeks, and for continuation, the maintenance injections were given once a month. The safety is graded according to The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System.
Results: The safety data of 3397 injections were analyzed. The total numbers of systemic reactions were 6 or 0.17% of all injections, all of them in the up-dosing phase. Of this, two were classified as immediate reactions and four as late-phase reactions. Of all systemic reactions, four were classified as grade 1 reaction and two as grade 2 reaction. Grade 3, 4 or 5 reactions did not occur. The local hypersensitive reactions were 28 or 0.82% of all injections; 42.8% of them were in the maintenance phase.
Conclusions: In this study, the safety of cluster immunotherapy with grass pollen allergens is demonstrated for application in children.
146 Omalizumab - One year experience in the treatment of severe atopic dermatitis
A. M. Mendes, A. C. C. Costa, S. Luz, E. Pedro, M. Pereira-Barbosa
Santa Maria Hospital, Lisbon, Portugal
Rationale: Omalizumab is a humanized monoclonal anti-IgE antibody that interrupts the allergic cascade which suggests that it can be effective in the treatment of several allergic conditions, including atopic dermatitis (AD). We describe 1 year follow-up of four patients with severe AD and high levels of total IgE, successfully treated with omalizumab.
Methods: Four patients (2 males, 2 females; 24-year-old average) with severe AD, allergic respiratory disease, and high levels of IgE (> 2000 UI/L) not responding to conventional therapies were proposed for omalizumab treatment. They were evaluated for SCORing Atopic Dermatitis (SCORAD) index and daily/rescue medication before, during, and after treatment. Omalizumab was administrated subcutaneously at 375 mg dose every 2 weeks for a year.
Results: Before treatment all patients were medicated with anti-H1 and H2 antihistamine (maximum daily dose), montelukast 10 mg/day, topical and oral steroids (average dose: 20 mg/day), and topical primacrolimus. Three patients were also medicated with cyclosporine and one of them was previously medicated with intravenous immunoglobulin G (1000 mg/kg/month) with no response. After 1 year, all patients improved although the onset for initial improvement was variable. The daily/rescue medication decreased in both dose and number of drugs. Systemic steroids were stopped with no relapse of symptoms. The SCORAD index was 66, 7 average at the beginning and 24, 4 after 1 year treatment. The patients did not experience adverse side effects.
Conclusions: Our data suggests that omalizumab may be a safe and effective alternative in the treatment of severe atopic dermatitis in allergic patients.
L17 Sequential IgE-targeted therapy combining immunepheresis and omalizumab in patients with severe atopic dermatitis and grossly elevated total serum IgE Levels-A pilot trial
A. Zink, A. Gensbaur, M. Zirbs, F. Seifert, I. Leon Suarez, J. Liptak, L. Eichhorn, A. Onken, M. Mempel, J. Huss-Marp, R. Hein, J. Ring, M. Ollert
Department of Dermatology and Allergy, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany
Rationale: To evaluate the role of IgE in atopic dermatitis (AD) by combining immunoglobulin (Ig)-apheresis and anti-IgE-antibody omalizumab to reduce IgE in patients with severe, therapy-refractory AD and grossly elevated IgE levels.
Methods: Investigator-initiated open-label pilot trial was used, treating 10 patients with Ig-apheresis prior to regular subcutaneous administration of 450 mg omalizumab every 2 weeks for 6 months followed by a 6 month follow-up. On every visit, total and free IgE and thymus and activation regulated chemokine (TARC) (CCL17) were quantified and the severity of AD documented by standardized photos as well as rated by SCORing Atopic Dermatitis (SCORAD) and by the patients' personal evaluation on a severity and pruritus-scale.
Results: Before starting treatment, IgE-levels ranged from 3728 to 69,872 kU/L. IgE-levels were seen to be reduced significantly after the Ig-apheresis and continuously drop in all patients during the anti-IgE therapy (reaching free IgE levels <150 kU/L in 5/10 and <1000 kU/L in 9/10 patients). A reverse trend was observed during the follow-up period. Parallel, a clear improvement of AD was seen during the treatment period in all patients followed by an aggravation during follow-up (SCORAD, pruritus, severity scale, TARC). Two patients dropped out after initial improvement due to acute exacerbation despite anti-IgE therapy and one patient was lost due to lack of compliance.
Conclusions: The sequential combination of Ig-apheresis and omalizumab is suitable to reduce grossly elevated serum IgE levels and improve clinical symptoms of severe refractory AD. Due to the limited number of patients included and the open-label design in our pilot trial, further studies are needed to strengthen this conclusion.
905 Comparison of skin prick testing and ImmunoCAP testing in the diagnosis of cat allergy
B. D. Robertson, MD, K. K. McKinney, J. W. Cole, M. R. Nelson, S. M. Gada, S. S. Laubach
Walter Reed National Military Medical Center Bethesda, Bethesda, MD
Background: Cat-specific serum IgE levels are sometimes used to augment or replace skin-prick testing (SPT) in the diagnosis of allergic rhinoconjunctivitis. The purpose of this study is to compare SPT and the cat-specific ImmunoCAP test in the diagnosis of cat allergy.
Methods: Subjects between the ages of 18 and 55 were enrolled in the study based on the presence or absence of naso-ocular symptoms in the presence of a cat. All subjects underwent SPT to cat and had cat-specific serum IgE measurement by ImmunoCAP (Phadia Ab, Uppsala, Sweden). Subjects then underwent a conjunctival challenge to standardized cat extract. A positive cat ImmunoCAP test was defined as a level >0.35 kU/L. True positives were defined as having a history of cat allergy symptoms and a positive conjunctival challenge, while true negatives lacked symptoms of cat allergy and were challenge negative.
Results: 13 true positive and 31 true negative subjects were identified. All (13/13) true positives had a positive SPT, and 29/31 true negatives had a negative SPT (Sensitivity: 100%; Specificity: 94%; PPV: 87%; NPV: 100%). 41 of the 44 subjects had serum available. Most (9/13) true positives had a positive cat ImmunoCAP test, and all (28/28) of the true negatives had a negative cat ImmunoCAP test (Sensitivity: 69%; Specificity: 100%; PPV: 100%; NPV: 87.5%).
Conclusion: SPT is more sensitive but less specific than ImmunoCAP testing when evaluating patients for cat allergy. The high sensitivity of SPT makes it more effective in ruling out cat allergy.
938 Ragweed allergy immunotherapy tablet reduces nasal and ocular symptoms of allergic rhinoconjunctivitis over the peak ragweed pollen season in North America
G. Berman 1 , H. Nolte 2 , J. Maloney 2 , P. Creticos 3 , A. Cheema 4 , A. Kaur 2 , J. Hebert 5
1 Minneapolis Allergy & Asthma Specialists, Minneapolis, MN, 2 Merck Research Laboratories, Kenilworth, NJ, 3 Johns Hopkins University School of Medicine, Baltimore, MD, 4 Alpha Medical Research, Mississauga, ON, CANADA, 5 Centre de Recherche Appliquee en Allergie de Quebec, Quebec, QC, CANADA.
Rationale: Peak season nasal and ocular symptoms of allergic rhinoconjunctivitis (ARC) are bothersome and can profoundly impact quality of life. The effects of sublingual ragweed allergy immunotherapy tablet (AIT) on nasal and ocular symptoms were investigated in North American ragweed allergic adults with or without asthma.
Methods: 565 adults were randomized to daily ragweed AIT 6 or 12 Amb a 1-U (Amb) or placebo. Treatment was initiated approximately 4 months before and continued throughout ragweed season (RS). Daily four nasal and two ocular symptoms were assessed on a scale from 0 (no symptoms) to 3 (severe). The peak RS was defined as the 15 consecutive days with the highest 15-day moving average pollen count.
Results: The ragweed AIT 12 Amb a 1-U and 6 Amb a 1-U groups showed mean improvement in total nasal scores compared to placebo of 14.8% (difference: 5-0.58 points; P<0.03) and 11.7% (difference: 5-0.46 points; P<0.09), respectively during peak RS. Total ocular scores revealed improvements of 21.8% (difference: 5-0.37 points; P<0.01) and 18.9% (difference: 5-0.32 points; P<0.03) for the 12 Amb a 1-U and 6 Amb a 1-U doses. Furthermore, a significant effect (P<0.05) on individual symptoms was noted for 12 Amb a 1-U dose on watery and itchy eyes, runny nose, and sneezing. Treatment with ragweed AIT was well tolerated with no observed difference between 6 and 12 Amb. There were no reports of systemic allergic reactions.
Conclusions: These results demonstrate that once-daily administration of ragweed AIT effectively treats the nasal and ocular symptoms of ragweed-induced ARC.
940 Diesel exhaust particles induce cysteine oxidation and S-glutathionylation in house dust mite induced murine asthma
G. B. Lee 1 , E. B. Brandt 2 , A. M. Gibson 2 , T. D. Le Cras 2 , L. S. Brown 3 , A. M. Fitzpatrick 3 , G. K. Khurana Hershey 2
1 University of Louisville School of Medicine, Louisville, KY, 2 Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 3 Emory University School of Medicine, Atlanta, GA.
Rationale: Diesel exhaust particle (DEP) exposure enhances allergic inflammation and has been linked to the incidence of asthma. Oxidative stress on the thiol molecules cysteine (Cys) and glutathione (GSH) can promote inflammatory host responses. We hypothesized that DEP exposure would alter the Cys or GSH oxidation-reduction state in the asthmatic airway.
Methods: Bronchoalveolar lavage fluid was obtained from a house dust mite (HDM)-induced murine asthma model exposed to DEP. GSH, glutathione disulfide (GSSG), Cys, cystine (CySS), and s-glutathionylated cysteine (CySSG) were determined by high pressure liquid chromatography.
Results: Compared with HDM exposure alone, DEP co-administered with HDM decreased total Cys (0.058 mM vs. 0.024 mM, P < 0.001), increased CySS (0.0043 mM vs. 0.025 mM, P < 0.0001), and increased CySSG (0.11 mM vs. 0.21 mM, P < 0.05) without significantly altering GSH or GSSG.
Conclusions: DEP exposure promotes oxidation and s-glutathionylation of cysteine amino acids in the asthmatic airway, suggesting a novel mechanism by which DEP may enhance allergic inflammatory responses.
864 Children's food allergies: Development of the food allergy adaptation and management scale
M. D. Klinnert 1,2 , D. Atkins 1,2 , D. Fleischer 1,2 , E. L. McQuaid 3 , J. Robinson 1,2 , J. O. Hourihane 4 , S. Cohen 1 , H. Fransen 1
1 National Jewish Health, Denver, CO, 2 University of Colorado School of Medicine, Aurora, CO, 3 Brown School of Medicine, Providence, RI, 4 University College, Cork, Ireland
Rationale: Families of children with FA are challenged to maintain a positive quality of life. Existing measures of families' adaptation to FA fail to assess whether coping strategies that families use result in balanced adaptation.
Methods: A semi-structured family interview was developed and rating scales were constructed on seven dimensions of FA management (FAMComposite), child anxiety (CAnx), mother anxiety (MAnx), and overall balanced integration (BI). Interviews conducted with 40 parents and children, aged 6_12, with physician-documented food allergies were video-recorded. Psychosocial researchers viewed and rated interviews for FAMComposite, C&MAnx, and BI. Validation measures included global ratings by physicians for families' food avoidance (P-FFA) and reaction response management (P-RRM), parent demonstrations of self-injectable epinephrine (Epi-Demo), parent and child anxiety questionnaires (STAI), food allergy impact (FAIS), and Food Allergy QoL Parent Burden (FAQLPB).
Results: Children were 8.6 (SD: 51.7) years old, 73% male, 83% Caucasian, and allergic to 3.3 (SD: 51.8) foods. Inter-rater reliability was excellent for FAMAS scales (ICC range: 0.91-0.98) and physician ratings (ICC: 50.98). FAMComposite correlated with P-FFA (r50.88 , P<0.0001) and P-RRM (r50.85, P<0.0001). Mean FAMComposite was higher for parents passing Epi-Demo (t(38)5-2.18, P<0.04). CAnx correlated with child anxiety (r50.48, P<0.002); MAnx did not correlate with mothers' self-reported anxiety. BI correlated at trend levels with FAIS stress subset (r5-0.33, P50.06) and FAQLPB (r50.29, P<0.07).
Conclusions: Preliminary analyses of the FAMAS strongly support validity of the FAMComposite and largely substantiate the negative influence of family anxiety and the positive influence of balanced integration. The validated FAMAS will facilitate assessment of family adaptation to children's food allergies.
866 Food allergy is an independent risk factor for decreased lung function in children
A. M. Singh 1 , R. Kumar 1 , L. M. Arguelles 1 , D. Caruso 1 , X. Wang 2 , J. A. Pongracic 1
1 Northwestern Feinberg School of Medicine, Chicago, IL, 2 Johns Hopkins Bloomberg School of Public Health, Baltimore
Rationale: Food allergy (FA) is an early expression of the atopic march, a progression that may lead to the development of asthma. However, the effect of FA on pulmonary function (PF) is not known.
Methods: A total of 1066 children were enrolled as a part of a family-based FA cohort. Children were categorized as having FA by physician diagnosis with evidence of specific IgE and typical symptoms within 2 hours of food ingestion. Asthma was diagnosed by parent report of physician diagnosis. Spirometry was measured in accordance with ATS criteria. Multivariate linear regression controlling for confounding variables (male sex, socieconomic status, RSV hospitalization, parental asthma, household smoke exposure, and total IgE) was performed to evaluate independent and joint associations of FA and asthma on PF.
Results: Of the 1066 children enrolled, 402 (38%) had FA and 417 (39%) had asthma. After adjusting for relevant factors, children with asthma had decreased forced expiratory flow (FEF) 25-75% predicted compared to children without asthma (-6.77±1.71%, P<0.001), but no difference in FEV 1 % predicted. Univariate analysis of multiple food allergies on PF also demonstrated lower FEF 25-75% predicted (-5.68±2.3%, P<0.01), while food sensitization alone had no effect. Interestingly, multiple food allergies with asthma had a combined effect with a decrease of -10.22±2.64% FEF 25-75% predicted (P<0.0001). There was no effect in children with asthma and one food allergy or in children without asthma and multiple food allergies.
Conclusion: Having multiple food allergies is an independent risk factor for decreased PF among children with asthma, highlighting the need for close clinical follow-up and improved intervention strategies for these patients.
879 Similar repeated sequences may account for cross reactions caused by many different nuts
S. J. Maleki 1 , S. S. Teuber 2 , C. H. Schein 3
1 US Department of Agriculture, New Orleans, LA, 2 University of California, Davis, School of Medicine, Davis, CA, 3 University of Texas Medical Branch, Galveston, TX
Rationale: Many peanut allergic individuals also have allergies to tree nuts. Our previous work has shown that the property distance (PD) scale in structural database of allergenic proteins (SDAP) can identify similar IgE-binding areas that may be important for cross-reactivity between allergens.
Methods: A cluster of repeat sequences in the N-terminal prosequence of the walnut allergen Jug r 2 was identified and a consensus sequence prepared from the repeats. A peptide from the consensus was used to generate antibodies in chickens. Western blotting was used to identify allergens in extracts from nuts recognized by the chicken antibodies, and by serum IgE from patients allergic to peanuts, walnuts, and almonds. Proteins in the reactive bands were identified by mass spectroscopy.
Results: Searching the SDAP using the PD tool with the consensus peptide sequence revealed many potential IgE epitopes with similar physicochemical properties in nut allergens, including several 7S, 2S, and 11S albumins. The antibodies to the consensus peptide recognized proteins of the appropriate size to these proteins in various nut extracts. Many of the proteins that bound the consensus peptide antibodies were identified by mass spectroscopy and recognized by IgE in the sera of patients with documented clinical cross-reactivity.
Conclusions: A repeated sequence motif, summarized by our consensus peptide, is common to many different allergenic proteins from nuts and seeds. The repeat may be a relic of a very ancient storage protein that has been conserved in various forms in nut proteins, perhaps because of antifungal properties.
878 Monoclonal antibodies for defining conformational epitopes in Ara h 2 and Ara h 6
J. Glesner 1 , S. Wuenschmann 1 , A. Koid 1 , G. A. Mueller 2 , L. C. Pedersen 2 , M. D. Chapman 1 , A. Pomes 1
1 INDOOR Biotechnologies, Inc., Charlottesville, VA, 2 National Institute of Environmental Health Sciences, Research Triangle Park, NC
Rationale: In addition to linear B-cell epitopes, strong evidence of the presence of conformational epitopes on peanut allergens exists. The goal was to obtain monoclonal antibodies (mAb) against Ara h 2 and Ara h 6 for defining conformational epitopes by X-ray crystallography.
Methods: Natural Ara h 2 and Ara h 6 were purified from peanut extracts. A panel of mAb (n5110) was raised against both allergens. A recombinant fusion protein of maltose-binding protein (MBP) attached to Ara h 2 was expressed in E. coli. ELISA was used to test recognition of the three allergen molecules by mAbs. IgE inhibition assays were performed using mAb or the allergens as inhibitors.
Results: The antibodies showed four main epitope specificities by direct binding to the three allergens: 1) 43% were cross-reactive, 2) 23% bound only the two Ara h 2 forms, 3) 8% bound only natural Ara h 2, recognizing an epitope covered by MBP, and 4) 1% bound only Ara h 6. Selected anti-Ara h 2 mAb1C3 and 1C4 recognizing only natural Ara h 2 inhibited 40-50% IgE antibody binding to natural Ara h 2. The strongest inhibition (80%) was observed for mAb2B6, which recognizes a crossreactive epitope, not masked by MBP. The MBP-construct allowed to distinguish if mAb bound an epitope masked by MBP or not, and assess the relevance of the allergen N-terminus for IgE antibody binding.
Conclusions: A panel of mAb interfering with IgE antibody binding was raised against peanut allergens and is a valuable tool for defining allergen-specific and cross-reactive conformational epitopes.
897 Exhaled NO may predict development of allergic rhinitis in children
Y. Rha 1 , H. Ko 1 , S. Choi 2
1 Kyung Hee University Hospital, Seoul, Republic of Korea, 2 Kyung Hee University Gandong Hospital, Seoul, Republic of Korea
Rationale: As a non-invasive parameter of lower airway inflammation, fraction of exhaled nitric oxide (FENO) concentration has been known to be related to bronchial hyperreactivity in asthma patient. FENO may be increased in atopy-related diseases (e.g. allergic rhinitis) but relationship of FENO and development of allergic rhinitis in asthma is unknown. The aim of this study was to investigate whether measurement of FENO in asthma children can predict development of allergic rhinitis.
Methods: A total of 53 children with mild to moderate persistent asthma aged from 5 to 15 years who were measured with FENO, total eosinophil count, and IgE were included. FENO was measured through a chemiluminescence analyzer. Prospectively, the patients were followed after 6 years by interview with questionnaire and FENO levels of the patient who developed allergic rhinitis (allergic rhinitis group and who do not manifest allergic rhinitis (control group) were evaluated.
Results: There were no difference of peripheral blood total eosinophil count, serum IgE, age, sex, family history, history of atopic dermatitis, or degree of asthma severity between the allergic rhinitis group and the control group. FENO was significantly higher in the allergic rhinitis group compared to the control group (29.4624.6 parts per billion [ppb] vs. 13.6611.8 ppb; P < 0.003).
Conclusions: Measurement of FENO can be a useful tool to predict to predict development of allergic rhinitis in asthmatic children.
795 Relationships between airway hyperresponsiveness to methacholine, blood eosinophil markers and fraction of exhaled nitric oxide in asthmatic children
Y. Yoo 1,2 , S. Bauer 1 , K. S. La 1 , H. S. Seo 1 , S. C. Seo 2 , D. J. Song 1,2 , J. T. Choung 1,2
1 Department of Pediatrics, College of Medicine, Korea University, Seoul, Republic of Korea, 2 Environmental Health Center, Korea University Anam Hospital, Seoul, Republic of Korea
Rationale: Airway inflammation, airflow limitation, and airway hyperresponsiveness (AHR) are distinctive features of asthma. Eosinophilic inflammations in the airways are correlated with baseline lung function and AHR. Fractional concentration of exhaled nitric oxide (FENO) is one of the useful markers of eosinophilic airway inflammation in asthmatic patients.
Methods: Measurements of baseline pulmonary function and methacholine challenge tests were performed in 55 children with mild persistent to moderate asthma. They were followed up at the Allergy Clinic of Korea University Anam Hospital. Each subject was evaluated for serum total IgE, blood eosinophil counts, and serum eosinophil cationic protein (ECP). FENO levels were evaluated in two occasions, i.e., "at baseline" and the "just after challenge."
Results: The mean (range of 1 SD) post-methacholine challenge FENO level (25.7 ppb (13.8-47.9)) was significantly lower than the baseline level (36.3 ppb (20.9-63.1)) (P<0.001). FENO levels significantly correlated with the methacholine PC20 (r5-0.527, P<0.0001), blood eosinophil counts (r50.296, P<0.028), but not with the serum ECP levels (r50.174, P<0.203).
Conclusions: FENO, one of the surrogate markers in airway inflammation in asthmatics, may be decreased after repeated spirometry. The levels of FENO were found to be correlated with methacholine airway hyperresponsiveness and blood eosinophil counts in asthmatic children.
726 Efficacy of sublingual immunotherapy in a typical american practice
J. G. Sanchez, R. Garcia-Ibanez
The AllergiGroup, Tampa, FL
Rationale: We previously reported the impact of sublingual immunotherapy (SLIT) on quality of life (QOL) and we are now reporting on the effects of SLIT mixes on total symptom score (TSS) of polysensitized patients. These results were then compared with those of a small group of patients receiving cluster subcutaneous immunotherapy (SCIT).
Methods: Total symptom score is comprised of nine domains with values ranging from 0 to 3 (0-5 none, 1-5 mild, 2-5 moderate, 3-5 severe), with a maximum score of 27. Each was calculated at every office visit. Statistical analysis was then performed via a paired t-test in StatPlus on the baseline TSS, TSS at 3 months, and TSS at 1 year.
Results: Analysis showed highly significant decrease in the mean TSS after 3 months and after 1 year. The mean TSS reduction after 3 months of SLIT and SCIT are (n: 556, m: 5-6.99, s.d.: 56.82, 95% CI: -5.17 to -8.82), P<0.00001) and (n: 54, m: 5-5 , s.d.: 52.68, 95% CI: -2.38 to -7.62), P<0.033), respectively. The reduction of TSS after 1 year (n: 556, m: 5-7.95, s.d.: 57.11, 95% CI: -6.04 to -9.85, P<0.00001) showed statistical improvement among patients.
Conclusions: These results show a significant impact of SLIT and SCIT mixes on the symptomatic load of polysensitized patient populations. The use of SLIT mixes may be a feasible alternative in a typical American practice.
727 Incidence of respiratory tract infections in clinical trials of intravenous and subcutaneous immunoglobulin
J. S. Baggish 1 , M. Bexon 2 , M. Rojavin 1 , O. Zenker 3 , M. Berger 1
1 CSL Behring LLC, King of Prussia, PA, 2 CSL Behring AG, Berne, Switzerland, 3 CSL Behring GmbH, Marburg, Germany
Rationale: In patients with primary immunodeficiency, the incidence of pneumonia tends to be higher at low doses and serum IgG trough levels (Orange et al. 2010, Clin Immunol, 137:21-30). The influence of dose and IgG trough levels on the incidence of more benign respiratory infections, such as bronchopulmonary infection (BPI) and sinusitis, has not been reported.
Methods: We conducted an analysis evaluating the rate of respiratory infections (pneumonia, BPI, and sinusitis) in relation to IgG doses and serum IgG trough levels. Pooled data of 392 patients from eight CSL Behring trials of intravenous (Sandoglobulin NF Liquid, Privigen) or subcutaneous (Vivaglobin, Hizentra) IgG were analyzed.
Results: Seventeen patients experienced pneumonia, 90 patients had BPI, and 101 patients had acute episodes of sinusitis. Patients with pneumonia tended to have lower-dose IgG treatments (median of individual median: 116 mg/kg/week) and achieved lower IgG trough levels (median of individual median: 8.7 g/L) than those with BPI (133 mg/kg/ week; 9.6 g/L) and sinusitis (144 mg/kg/week; 9.9 g/L).
Conclusions: We found an inverse relationship between IgG doses and serum trough levels and the incidence of pneumonia. Patients experiencing BPI and sinusitis had received higher IgG doses than patients experiencing pneumonia and the incidence of these infections was not related to dose or IgG trough level. Higher IgG doses and trough levels may be required to prevent pneumonia, which tends to be the most severe respiratory infection, in patients with primary immunodeficiency.
732 Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: Looking at the published evidence
P. Demoly 1 , L. Cox 2 , T. B. Casale 3 , P. Moingeon 4 , M. A. Calderon 5
1 Allergy Division, Pneumology Department, INSERM U657, Hpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France, 2 Department of Medicine, Nova Southeastern University, davie, FL, 3 Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, NE, 4 Stallergenes, Antony, France, 5 Section of Allergy and Clinical Immunology, Imperial College-NHLI, Royal Brompton Hospital, London, United Kingdom
Rationale: In allergen immunotherapy, there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (a predominantly North American approach) or a single, clinically problematic allergen (a predominantly European approach).
Methods: We reviewed the literature on single- and multiallergen allergen immunotherapy in polysensitized and monosensitized patients.
Results: In individuals seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range: 50-80%) than monosensitization in both the USA and Europe. Hence, single allergen preparations will almost certainly have been clinically tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen SCIT and SLIT, polysensitized subjects benefited at least as much from single-allergen immunotherapy as monosensitized patients did. There were no obvious safety profile differences between polysensitized and monosensitized participants. A recent trial of single-allergen SLIT versus multiallergen SLIT in predominantly polysensitized patients concluded that the co-administration of multiple allergens may have interfered with the effectiveness of the single-allergen timothy extract. Other studies suggest that multiallergen SCIT is less effective in polysensitized patients than single-allergen allergen immunotherapy is in monosensitized subjects and that higher allergen doses are needed in multiallergen SCIT.
Conclusions: According to an evidenced-based analysis, single allergen preparations (grass pollen extracts) are clearly efficacious and safe in polysensitized participants. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients needs more supporting data in large clinical trials to validate it as a treatment option. More work is also required to determine whether single- and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized subjects.
770 Relationship between environmental phenols and aeroallergen and food allergies in the USA: Results from the National Health and Nutrition Examination Survey 2005-2006
N. Vernon, E. Jerschow, S. Jariwala, G. de Vos, D. Rosenstreich
Monte- fiore Medical Center, Bronx, NY
Rationale: Previous research supports a possible link between environmental pollution and allergic conditions. Vitamin D deficiency has been associated with higher levels of allergic sensitization in children and adolescents. We hypothesized that exposure to environmental phenols is associated with an increased risk of sensitization to food and aeroallergens, and that the association of phenol exposure with allergies would differ among people with low versus normal levels of vitamin D.
Methods: Data was extracted from 2548 participants in the National Health and Nutrition Examination Survey 2005-2006. Phenolic compound levels were measured in urine. Food and aeroallergen-specific IgE levels were measured in serum. A sample weight-adjusted chi-square test was used to determine the association between phenol exposure and the sensitization to food or aeroallergens. Adjustment was made for vitamin D levels (<30 ng/ml and >30 ng/ml).
Results: Exposure to 1 or more phenols was associated with the presence of food allergy if vitamin D level was <30 ng/ml (OR: 51.8, 95% CI: 1.6-1.96, P<0.001). There was no significant association between phenol exposure and increased aeroallegen-specific serum IgE levels.
Conclusions: Exposure to environmental phenols is associated with the presence of food allergies in individuals with low levels of vitamin D. There was no significant association between phenol exposure and food allergies in individuals with normal vitamin D levels.
776 Genetic variants associated with asthma and related phenotypes are also risk factors for food allergy
C. Vergara 1 , N. Rafaels 1 , L. Gao 1 , C. Foster 1 , M. Campbell 1 , J. Potee 1 , R. Lewis 1 , T. H. Beaty 2 , S. Jones 3 , A. W. Burks 4 , S. Sicherer 5 , R. A. Wood 6 , D. Stablein 6 , L. A. Beck 7 , H. A. Sampson 8 , A. H. Liu 8 , D. Y. Leung 7,8 , R. A. Mathias 1,9 , K. C. Barnes 1
1 Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University, Baltimore, 2 Department of Epidemiology, Bloomberg School of Public Health, JHU, Baltimore, 3 University of Arkansas for Medical Sciences, Little Rock, AR, 4 Duke University Medical Center, Durham, NC, 5 Mount Sinai School of Medicine, New York, NY, 6 The EMMES Corporation, Rockville, 7 Department of Dermatology, University of Rochester Medical Center, Rochester, NY, 8 Department of Pediatrics, National Jewish Health, Denver, CO, 9 Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University, Baltimore
Rationale: The high co-morbidity of food allergy (FA) and sensitization (FS) with other IgE-mediated diseases, such as asthma, suggest common genetic determinants. We tested this hypothesis for a set of GWAS-identified candidate genes for asthma/atopy in FA/FS.
Methods: 359 single nucleotide polymorphisms (SNPs) representing 46 asthma/total IgE GWAS-identified genes were genotyped (Illumina BeadExpress) in a discovery cohort (Consortium of Food Allergy Research, CoFAR:NIAID) of 317 European-American (EA) and 70 African-American (AA) children with atopic dermatitis (AD) and clinical and/or serologic evidence of FA (milk/egg/peanut) and 270 EA and 332 AA non-FA-non-AD controls. Replication was sought in Atopic Dermatitis Research Network (ADRN:NIAID) participants: 139 EA and 84 AA AD cases characterized for FS using a multiallergen-specific Phadia ImmunoCAP tests (FX5E) and compared to 114 EA and 107 AA AD cases without FS, respectively. Association tests were conducted within a logistic framework including relevant covariates.
Results: In CoFAR, seven SNPs were significantly associated with FA risk in EA (Bonferonni-corrected-P-values<_2.9x10 -5 ). Six of these mapped to GPR126, PDE4D, PTCH1, GSTCD, and IL13. Another 17 SNPs representing seven genes (DENND1B, IL1R1, SMAD3, IL-10, ADAM33, RAD50, and ADCY2) were associated at P<0.0005-0.041 in EA and AA, but failed Bonferonni corrections. A gene-based-replication for FS was observed for PDE4D in EA and AA of the AD ADRN cohort with lower statistical evidence (uncorrected P<0.002).
Conclusions: Genetic variants in genes associated with asthma and high total IgE levels (i.e., PDE4D) may be risk factors for FA/FS in AD individuals.
657 Filaggrin mutations are associated with an increased risk of infantile food allergy and sensitization
T. Tan 1,2 , J. A. Ellis 1,3 , J. J. Koplin 1 , P. E. Martin 1,2 , T. D. Dang 1,2 , M. C. Matheson 4 , S. Dharmage 1,4 , A. Lowe 1,4 , M. Tang 1,5 , M. Robinson 5 , A. Ponsonby 1 , N. Osborne 6 , D. Hill 1 , K. J. Allen 1,5
1 Murdoch Childrens Research Institute, Melbourne, Australia, 2 Department of Paediatrics, University of Melbourne, Melbourne, Australia, 3 Department of Physiology, University of Melbourne, Melbourne, Australia, 4 Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Australia, 5 Department of Allergy and Immunology, Royal Children's Hospital, Melbourne, Australia, 6 European Centre for Environment and Human Health, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, United Kingdom
Rationale: Filaggrin is central to skin barrier maintenance and filaggrin (FLG) mutations increase the risk of eczema, a condition associated with IgE-mediated food allergy. Recently, FLG mutations were shown to increase the risk of peanut allergy although other foods were not assessed. We aimed to determine whether FLG mutations increase the risk of challenge-proven food allergy (egg, peanut, and sesame allergy) in a population cohort of 1-year-old infants.
Methods: 5302 one-year-old infants recruited from the population underwent skin prick tests (SPT) for egg, peanut, and sesame and those sensitized underwent oral food challenge (OFC) to those foods. DNA from 627 Caucasian infants (n = 5308 with challenge-confirmed food allergy to peanut, egg, and sesame; n = 5213 with positive SPT but negative OFC; and n = 5106 with negative SPT and negative OFC) were genotyped for five FLG mutations (R501X, 2282del4, R2447X, S3247X, and 3702delG) using Sequenom MassARRAY. Logistic regression was used for case-control analyses comparing infants with negative SPT and OFC (controls) with sensitized and allergic infants (cases).
Results: The presence of at least one of the above FLG mutations was associated with an increased risk of developing both food sensitization (OR: 52.9; 95% CI: 51.1-7.3) and challenge-confirmed food allergy (OR: 52.8; 95% CI: 51.1-7.4).
Conclusions: FLG mutations increase the risk of food allergy and food sensitization to egg, peanut, and sesame in infants recruited from the general population. Further work elucidating the role of eczema in the association between FLG mutations and food sensitization/allergy is ongoing.
659 High-molecular-weight glutenin, Tria 26, is an important allergen component in children with immediate allergy to wheat
C. Eriksson 1 , M. Lundberg 2 , A. Tanka 3 , H. Takahashi 4 , E. Morita 4 , K. Ito 5
1 Thermo Fisher Scientific, ImmunoDiagnostics, R&D, Uppsala, Sweden, 2 Thermo Fisher Scientific, ImmunoDiagnostics, Uppsala, Sweden, 3 Thermo Fisher Scientific, ImmunoDiagnostics, Tokyo, Japan, 4 Department of Dermatology, Shimane University, Izumo, Japan, 5 Aichi Childrens Health and Medical Center, Obu, Japan
Rationale: Omega-5 gliadin (Tria 19) is a major allergen component in children with immediate allergy to ingested wheat. A fraction of patients with immediate wheat allergy however lack specific IgE (sIgE) to omega-5 gliadin. The aim of this study was to evaluate the importance of the wheat component high-molecular-weight (HMW) glutenin (Tria 26) in immediate wheat allergy and in particular for those patients lacking sIgE to omega-5 gliadin.
Methods: Recombinant full-length HMW glutenin was attached to the ImmunoCAP matrix. Sera from 50 Japanese children with immediate wheat allergy were analyzed for sIgE to HMW glutenin and to omega-5 gliadin.
Results: Sixty percent (30/50) of the children with immediate wheat allergy had sIgE to the rHMW glutenin and 80% (40/50) had sIgE to omega-5 gliadin. Six out of the 10 children (60%) without detectable levels of sIgE to omega-5 gliadin had sIgE to HMW glutenin.
Conclusions: In this study, HMW glutenin and omega-5 gliadin are both major allergen components for Japanese children with immediate allergy to wheat. Ninety-two percent of the patients have sIgE to either omega-5 gliadin or HMW glutenin or both. Simultaneous measurement of sIgE to omega-5 gliadin and HMW glutenin could thus be a helping tool in diagnosis of immediate allergy to wheat.
431 In mice sensitized to milk, epicutaneous immunotherapy prevents further sensitization to peanut or house dust mite
L. Mondoulet 1 , V. Dioszeghy 1 , E. Puteaux 1 , M. Ligouis 1 , V. Dhelft 1 , C. Dupont 2 , P. Benhamou 1
1 DBV Technologies, Bagneux, France, 2 Hopital Necker, Paris, France.
Rationale: Epicutaneous immunotherapy (EPIT) to milk was proved safe and efficacious in children with milk allergy. This study evaluated in a model of milk sensitized mice if milk EPIT might prevent from further sensitization to other allergens.
Methods: After oral sensitization, BALB/c mice were treated with EPIT (milk-Viaskin or sham-Viaskin) and then further sensitized to peanut or house dust mite (HDM). After further sensitization to peanut, mice were exposed to a sustained peanut regimen, known to induce esophageal eosinophilic infiltration correlated to Th2 cytokines mRNA expression. After further sensitization to HDM, mice were challenged by aerosol and tested by BAL fluid content and plethysmography. Specific antibodies to milk, peanut, and HDM were monitored. Naive mice were included.
Results: Milk EPIT was efficient, with a significant increase of sIgG2a, 1.2560.35 vs 0.0560.02 mg/ml (EPIT vs Sham, P<0.05) and a significant decrease of Th2 cytokines secreted by milk-reactivated splenocytes (vs. Sham, respectively, IL-4: 17 pg/ml vs 86 pg/ml, P<0.05; IL-5: 14 pg/ml vs 153 pg/ml, P<0.05; IL-13: 11 pg/ml vs 159 pg/ml, ns). After further sensitization, only the milk-EPIT group showed a significant increase of sIgG2a to PPE or HDM and decrease of sIgE for PPE. Also, the milk-EPIT group did not exhibit any increase in (1) esophageal eosinophilic infiltration after peanut exposure, 3 eosinophils/mm 2 vs 27 eosinophils/mm 2 (sham, P<0.01), and vs 4 eosinophils/mm 2 (na€ıve, ns), (2) Penh values after HDM aerosol challenge, AUC512164.9 vs 204619.6 (sham, P <0.01) and vs 11764.0 (naive, ns).
Conclusions: In mice sensitized to milk, EPIT suppressed the immune response to further sensitizations by other allergens.
653 Prenatal exposure to nut allergens and risk of childhood nut sensitization
J. T. Hsu 1 , S. A. Missmer 2 , M. C. Young 1 , K. F. Berry 2 , F. J. Twarog 1 , I. Borras 1 , M. D. Hornstein 2 , L. C. Schneider 1
1 Children's Hospital Boston, Boston, MA, 2 Brigham and Women's Hospital, Boston, MA
Rationale: Allergic diseases have increased four-fold in the last 10 years. Prenatal exposures, including maternal diet and medications, may account for some of this increase. In the USA, progesterone for fetal support in assisted reproduction is commonly formulated in peanut or sesame oil; it is unknown whether this increases the child's risk to peanut or tree nut allergy.
Methods: Parents of children seen in the Allergy Program at Children's Hospital Boston and two affiliated practices between May 2005 and October 2009 completed questionnaires on reproductive methods, prenatal exposures, and child's dietary and allergic history. A total of 1272 completed questionnaires were returned. Child's medical record, allergy skin-prick test, and blood test results were reviewed. Odds ratios (OR) and 95% confidence intervals (CI) are from adjusted logistic regression models.
Results: There was no increased risk of peanut or tree nut sensitization in the children of mothers with history of infertility, in vitro fertilization, or use of progesterone-in-oil. First trimester maternal consumption of tree nuts was associated with a 60% higher OR of having a nut-sensitized child (95% CI: 51.01-2.51). A similarly increased OR was seen with first trimester maternal sesame seed ingestion (OR: 51.78; 95% CI: 51.08-2.92). The OR of nut sensitization were twice as high among children with asthma and environmental allergies.
Conclusions: Neither maternal infertility nor exposure to nut oils via progesterone support during assisted reproduction increased the odds of peanut or tree nut sensitization in the child. First trimester maternal ingestion of tree nuts and sesame seeds during pregnancy was associated with increased OR of nut sensitization in the child.
642 Delayed gastrointestinal symptoms after ingesting shrimp in the absence of IgE sensitization
R. Firszt, K. Sebastien, G. J. Gleich, L. A. Wagner
University of Utah, Salt Lake City, UT
Rationale: Shellfish allergy affects 2% of the adult US population. IgE-mediated reactions typically include immediate symptoms, such as urticaria, angioedema, dyspnea and, in some cases, anaphylaxis. There are, however, some patients who are able to consume shellfish, but later experience gastrointestinal symptoms with vomiting, abdominal cramping, and diarrhea. These patients resemble infants and young children with food protein-induced enterocolitis syndrome (FPIES).
Methods: In an ongoing study, 38 individuals with a clinical history of reactions to ingesting shrimp were recruited through fleact and newspaper advertisements. Percutaneous skin testing was performed using extracts of shrimp, crab, lobster, mollusks, and fish species with appropriate controls (Greer Laboratories, Lenoir, NC). Serum total and specific IgE levels were measured using ImmunoCAP.
Results: Nine (24%) of the shrimp-sensitive patients suffered delayed onset of gastrointestinal symptoms (range for onset of symptoms: 20 minutes to 4 hours). These patients were able to tolerate shrimp without immediate consequence and suffered only abdominal symptoms. Of these nine patients, only one had a positive percutaneous reaction to shrimp and this subject had a negative IgE antibody to shrimp. In total, 2/9 patients had IgE antibodies to shrimp. These patients differed strikingly from the IgE-mediated group who experienced immediate reactions.
Conclusions: Our data indicate that a surprisingly high proportion of patients reactive to shrimp experience gastrointestinal symptoms in the absence of IgE sensitization. Seemingly, the most comparable syndrome is FPIES with the exception that these are adults and their sensitivity appears to persist over time. Further investigation using double-blind, placebo-controlled food challenge (DBPCFC) and underlying mechanistic studies are ongoing.
641 Crustacean allergy: A new allergen inside cephalothorax?
N. Cancelliere, D. Guillen, S. Olalde, O. Caldern, T. Caballero, A. Fiandor, S. Quirse
Hospital La Paz, Spain, Spain
Introduction: Seafood contains many proteins, few of them allergenic. Tropomyosin is crustacean's main allergen. Other allergenic proteins have also been found: arginine kinase, myosin light chain, and sarcoplasmic calcium cross-linking protein, all of which are muscular proteins. In seafood allergy diagnosis there is generally a good agreement between medical history, skin-prick tests, and IgE measurements (ImmunoCAP, Phadia, Sweden) with commercial shrimp extract). However, there is a small group of patients with an unequivocally history of crustacean allergy in which the classical IgE tests are negative, hence a prick-prick test with a fresh shrimp is necessary. Moreover, symptoms seem to increase when the patient suck the crustacean's head.
Objective: To assess whether there are differences between the prick tests results performed with fresh seafood using separately the muscle and the interior of the cephalothorax in patients with both negative IgE measurements and skin-prick tests with commercial shrimp extract.
Method: Four patients were diagnosed with crustacean allergy showing positive prick test and negative ImmunoCAP. A prick-prick test with fresh seafood (shrimp and squat lobster) was performed in each patient, using separately the interior of the cephalothorax and the abdomen muscle.
Results: All patients showed positive prick-prick results with the interior of the cephalothorax, but only one was positive with the muscle.
Conclusion: It seems that allergens not present in commercial shrimp extracts are present inside the crustacean's cephalothorax, very likely not muscular proteins. The existence of such allergens would explain the fact that some patients only experience allergic symptoms when sucking the crustacean's head.
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