Indian Journal of Allergy, Asthma and Immunology

EDITORIAL
Year
: 2019  |  Volume : 33  |  Issue : 1  |  Page : 1--3

Homologous allergens: A regulatory and clinical perspective


SN Gaur 
 Department of Respiratory Medicine, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India

Correspondence Address:
Dr. S N Gaur
Department of Respiratory Medicine, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh
India




How to cite this article:
Gaur S N. Homologous allergens: A regulatory and clinical perspective.Indian J Allergy Asthma Immunol 2019;33:1-3


How to cite this URL:
Gaur S N. Homologous allergens: A regulatory and clinical perspective. Indian J Allergy Asthma Immunol [serial online] 2019 [cited 2019 Dec 8 ];33:1-3
Available from: http://www.ijaai.in/text.asp?2019/33/1/1/260169


Full Text

The last decade has ushered new data on the allergenic molecules. Allergens from identical protein families are now known to be present in different allergen sources and are labeled as homologous allergens. An important fact for such allergens is that they may be present among different sources, and their presence is not conditional to taxonomical relationship. These allergenic molecules express sequence identity and clinical cross-reactivity. This principle of homologous allergens was brought forward by Lorenz et al.[1] They also suggested that “classification of allergen sources in one homologous group on the basis of homology and cross-reactivity of allergens is more specific and satisfactory than mere taxonomic relationship.”[1]

The criteria to classify allergens as “Homologous allergens” is as follows:[1]

“The allergen sources have comparable physicochemical and biological properties, i.e., they derive from comparable tissues and therefore are alike in the overall composition of proteins, carbohydrates, lipids, enzymes, and water content”Demonstration of “cross-reactivity between the allergen sources shown by cross-reactivity of single allergens or the whole extracts”

The first criteria helps in differentiating separate allergens from the same source (e.g., wheat pollen allergens are different from wheat grain allergens; however, wheat pollen is homologous to many grass pollen). The second criteria of cross-reactivity is linked with homology of allergens belonging to identical protein families with a high degree of sequence identities at protein or cDNA level.[1] The proposed list of homologous allergens is captured in [Table 1].[1],[2] The allergens which have been categorized in [Table 1] are well studied in different geographies and are well characterized.{Table 1}

From the regulatory perspective for marketing authorization applications, “homologous allergens” fulfill the following criteria:[1]

Comparable physicochemical and biological properties of the source materialsCross-reactivity/structural homology of allergensIdentical formulation of the final products andIdentical production process of the allergen extracts.

For India, allergens such as the house dust mites (Dermatophagoides sp.), Pooideae grass pollen, and for mountainous regions, the birch group allergens are important. In recent years, several government schemes are promoting plantation of olive trees in the state of Rajasthan. Clinicians and researchers should evaluate the allergenic impact of olive in Indian context.

It should also be noted that data on homology of some Indian-specific allergens such as Holoptelea integrifolia, Prosopis juliflora, and others are missing.

 Regulatory Perspective



It is recognized that determination of all relevant parameters for the allergens within a given extract or a defined allergen extract mixture is impossible. Therefore, the concept of homologous allergens has been introduced and recognized.[2]

Within the homologous group, one member is selected as the representative species. Data (limited) from the representative allergen can be extrapolated to other members from the same groups. The extrapolated data can include data on quality, safety, and efficacy.[2]

Importantly, as noted above, some allergens are not included in the homologous allergens. For these, the data for quality, safety, and efficacy have to be provided for each individual product.[2]

 Clinical Perspective



For a clinician, the knowledge of homologous allergens can be utilized for formulating and prescribing allergen immunotherapy.

If a patient is allergic to allergens within a homologous group (such as Dermatophagoides species or Pooideae pollens), the use of a single course of AIT with a mixture of allergens that mimics natural exposure is recommended. Examples of such situations are:

Patient allergic to house dust mites of Dermatophagoides species:

›A mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae can be used.

Patient allergic to Pooideae (grass) pollen, such as Lolium perenne, Poa pratensis, and Phleum pratense:

›A mixture of the homologous grass allergens can be used.

If the patients are exposed and sensitized to allergen isoforms originating from two or more species in the group, they will develop antibody and T cell responses to both cross-reactive and noncross-reactive epitopes. Therefore, a mixture of the species will provide a broad spectrum of allergens identified by the patient and will lead to therapeutic responses.[3]

If patients recognize and react to nonhomologous allergens, the allergens should be given as individual allergens as there are no large evidences supporting the use of allergen mixtures. If mixtures are utilized, the following points can be kept in mind:[2],[3]

Do not use allergens with proteolytic activities in mixturesPerennial and seasonal allergens should not be mixedHymenoptera venoms should not be mixed with any other allergensVenoms from different genera should not be mixedPossible antigenic competition.

 Conclusion



Emerging evidences have let the scientific committees to focus on the concept of homologous groups. This concept is important for both regulators and clinicians who can utilize this information in decision-making algorithms.

References

1Lorenz AR, Lüttkopf D, May S, Scheurer S, Vieths S. The principle of homologous groups in regulatory affairs of allergen products – A proposal. Int Arch Allergy Immunol 2009;148:1-7.
2Committee for Medicinal Products for Human Use. Guideline on Allergen Products: Production and Quality Issues. EMEA/CHMP/BWP/304831/2007; 2008.
3Demoly P, Passalacqua G, Pfaar O, Sastre J, Wahn U. Management of the polyallergic patient with allergy immunotherapy: A practice-based approach. Allergy Asthma Clin Immunol 2016;12:2.