|Year : 2016 | Volume
| Issue : 2 | Page : 91-94
A cross-sectional study of clinico-immunological profile of systemic lupus erythematosus patients in a tertiary care centre in Mangalore
Neethu Kishor, Rekha Boloor, TK Sukumar
Department of Microbiology, Father Muller Medical College, Mangalore, Karnataka, India
|Date of Web Publication||5-Dec-2016|
Department of Microbiology, Father Muller Medical College, Kankanady, Mangalore - 575 002, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, which occurs frequently in women, mainly at childbearing age. This disease can affect any organ system; its presentation and course over time are highly variable. It is characterized by autoantibody response to nuclear and cytoplasmic antigens. Inadequate data on its clinico-immunological profile are available. The present study focuses on reevaluating clinical and immunological manifestations and also the management of SLE patients. Materials and Methods: The study was carried out in a tertiary care hospital for 2 years, i.e., from June 2014 to May 2016. Patients of all age groups fulfilling revised American College of Rheumatology Criteria (1997) was included in this study. Baseline investigations were done, and autoantibody profiling was done using immunoblot strips coated with 14 different antigens. Results: Over a period of 2 years, 40 patients were studied. The majority (85%) was females, and most of the patients were of the age group 15-30 years. Fever was the most common clinical manifestation (55%), followed by arthritis (33%) and dermatological manifestations (25%). Antinuclear antibody profile showed autoantibodies against nucleosomes in 19 patients (48%), followed by nRNP in 18 (45%), dsDNA in 17 (43%), Ro in 16 (40%), ribosomal P in 16 (40%), Sm in 13 (33%), and histones in 13 (33%) patients. Most of the patients (45%) were treated with a combination of corticosteroid and antimalarial. Conclusion: Clinical manifestations can vary between fever, arthritis, and skin rash to severe systemic involvement. The disease is more common in females especially during the second and third decade of life. Autoantibody profiling aids in supporting diagnosis and antimalarials along with corticosteroids are mainstay of treatment.
Keywords: Autoantibody profiling, clinico-immunological profile, immunoblot strips, systemic lupus erythematosus
|How to cite this article:|
Kishor N, Boloor R, Sukumar T K. A cross-sectional study of clinico-immunological profile of systemic lupus erythematosus patients in a tertiary care centre in Mangalore. Indian J Allergy Asthma Immunol 2016;30:91-4
|How to cite this URL:|
Kishor N, Boloor R, Sukumar T K. A cross-sectional study of clinico-immunological profile of systemic lupus erythematosus patients in a tertiary care centre in Mangalore. Indian J Allergy Asthma Immunol [serial online] 2016 [cited 2017 Apr 27];30:91-4. Available from: http://www.ijaai.in/text.asp?2016/30/2/91/195250
| Introduction|| |
Systemic lupus erythematosus (SLE) is an archetype of systemic autoimmune disease characterized by the production of a broad spectrum of autoantibodies.  Severity ranges from a mild disease with rash and arthritis to a devastating illness with renal failure and central nervous system involvement.  A review study conducted in Asia has shown the prevalence rate of disease from 30 to 50/100,000 population.  Another study conducted from rural India has shown a very low prevalence rate (3.2/100,000 population).  Due to the role of estrogen in etiopathogenesis of disease, SLE is more common in females, especially in childbearing age group as compared to males with a ratio ranging from 7:1 to 15:1.  More than 100 autoantibodies have been found in the sera of patients with SLE. Autoantibodies found in SLE patients are antinuclear antibody (ANA), antidsDNA antibody, and anti-extractable nuclear antigen (ENA) antibody. Anti-ENA antibodies include anti-smith (Sm), anti-ribonucleoprotein (RNP), anti-Ro and anti-La antibodies.  Antimalarial agents, specifically chloroquine and hydroxychloroquine are the mainstay of treatment for SLE, in combination with other immunomodulatory drugs. Their immunomodulatory and anti-inflammatory effects are associated with numerous beneficial effects on the outcomes of patients with SLE, including improvements in survival and remission rates, and reductions in disease activity, accrual of new disease-related damage and infection rates. 
Inadequate data on clinico-immunological manifestations pose a major barrier to further understand this disease. Most of the data available are from the western population. However, the immune status, individual response to disease and type of antibodies, vary from person to person, place to place, and population to population. In view of this, the present study focuses on reevaluating the clinical manifestations, management, and frequency of various autoantibodies found in patients with SLE in the Southern part of Karnataka.
| Materials and Methods|| |
Hospital-based observational descriptive study was carried out in a tertiary care hospital for 2 years, i.e., from June 2014 to May 2016. All patients, irrespective of age group, fulfilling the revised American College of Rheumatology Criteria (1997) for SLE and on whom autoantibody profiling has been done was included in the study. Patient details such as age, gender, and detailed history including chief complaints, duration of disease, and significant history was noted. A complete clinical examination was performed, and the patients were subjected to baseline investigations such as complete blood count, urine microscopic examination, 24 h protein excretion and renal function tests. Antibodies against nuclear antigens were analyzed using immunoblot strips coated with 14 different antigens (EUROIMMUN Medizinische Labordiagnostike AG) - nRNP, Sm, SS-A, SS-B, Scl-70, PM-Scl, Jo-1, CENP B, PCNA, dsDNA, nucleosomes, histones, ribosomal P-protein, and AMA-M2 from serum sample of patients. The test strips were coated with parallel lines of highly purified antigens. The patient samples for analysis are diluted 1:101 with sample buffer. In the first reaction step, diluted patient samples were incubated with the immunoblot strips. In case of positive samples, the specific IgG antibodies (also IgA and IgM) bound to the corresponding antigenic site. To detect the bound antibodies, a second incubation was carried out using an enzyme labeled anti-human IgG (enzyme conjugate) catalyzing a color reaction. After stopping the reaction using distilled water, the incubated test strips were evaluated using EUROLineScan software (EUROIMMUN Medizinische Labordiagnostika AG, Lubeck (Germany)). Based on the signal intensity, the results were interpreted. No signal was taken as negative, very weak band as borderline, medium to strong band (+, ++) as positive and very strong band with intensity comparable to control band (+++) as strong positive.
| Results|| |
Forty patients were studied in a period of 2 years, out of which, 34 (85%) were females. Female:male ratio was 6:1. The mean age of onset of disease was 29.8 years (range 9-69 years), and most of the patients between 15 and 30 years of age.
Fever was the most common clinical manifestation and presenting complaint (55%), followed by arthritis (33%) and dermatological manifestations (25%). Mucocutaneous manifestations in the form of skin rash, malar rash, photosensitivity, and oral ulcers were seen in 25%, 12.5%, 7.5%, and 15% of patients, respectively. Renal involvement manifesting as lupus nephritis was seen in 10 (25%) patients whereas proteinuria (>0.5 g/day) and hematuria were present in 58% and 25% of the patients, respectively. Hematological features were observed in 22 (55%) patients. Hemolytic anemia was noticed in 3 (7.5%), thrombocytopenia (<100,000/mm 3 ) in 19 (48%), and leukopenia (<4000/mm 3 ) in 6 (15%) patients [Table 1].
|Table 1: Clinical manifestations in patients with systemic lupus erythematosus (n=40)|
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ANA profile showed auto-antibodies against nucleosomes in 19 patients (48%), followed by nRNP in 18 (45%), dsDNA in 17 (43%), Ro in 16 (40%), ribosomal P in 16 (40%), Sm in 13 (33%), and histones in 13 (33%) patients [Figure 1].
Most of the patients with SLE, i.e. 18 patients (45%) were treated with a combination of a corticosteroid (prednisolone) and antimalarial (hydroxychloroquine), 10 (25%) with prednisolone alone, 9 (22.5%) with hydroxychloroquine alone, 2 (5%) with mycophenolate mofetil, and 1 (2.5%) with cyclophosphamide [Figure 2].
| Discussion|| |
In the present study, it was noticed that the disease was more common in female patients (85%) especially during the second and third decade of life with female:male ratio 6:1. The mean age of onset of disease was 29.8 years (range 9-69 years). These findings are consistent with another study carried out in Northern Kerala by Binoy et al.,  in which, out of the 75 patients evaluated, 70 were females. Furthermore, 55% of the patients were between 16 and 25 years of age. In another study by Kosaraju et al.,  out of the 48 patients studied, mean age of onset was 34.25 years (range 12-70 years) which is similar to this study in which mean age is 29.8 years. This study also observed female:male ratio as 15:1, with peak ratio in the age group of 21-30 years.
Fever was the most common clinical manifestation seen in this study group, i.e. in 55% of patients followed by arthritis (33%) and mucocutaneous manifestations (25%). However, Kosaraju et al.,  in his study in South Indian population observed arthritis was the most common (64.58%), followed by fever (58.33%) and skin rash (50%). Agrawal et al.,  in his study, in central rural India observed fever (82.8%) and malar rash (71.3%) as the most common clinical manifestations. Thus, varying clinical manifestations has been observed in different geographical locations in India, with dermatological manifestations observed comparatively less in South Indian population mostly owing to darker complexion [Table 2].
|Table 2: Cumulative incidence of clinical manifestations of systemic lupus erythematosus in comparison to other studies|
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In the present study, lupus nephritis was seen in 25% of patients similar to another study in South India  where renal involvement in the form of lupus nephritis was seen in 20.83% of patients. Comparable to this study, all patients with lupus nephritis were positive for dsDNA; confirming the fact that antibodies to dsDNA are strongly associated with renal involvement in SLE patients.
In this study, antibodies against nuclear antigens (IgG) analyzed using immunoblot strips coated with various antigens showed that autoantibodies were seen against nucleosomes (48%), followed by nRNP (45%), dsDNA (43%), Ro (40%), ribosomal P-protein (40%), Sm (33%), and histones (33%). Santhanam et al.  recorded anti-Sm in 49%, followed by anti-Ro, anti-dsDNA, and anti-U1RNP. ANA profile in yet another study in South India  showed positive reactions with dsDNA, RNP and Sm antigens, findings being consistent with the present study.
Antimalarial drugs, specifically chloroquine and hydroxychloroquine, have been gaining increased prominence in the treatment of patients with SLE either with or without renal involvement as a result of their excellent safety profile and increasing evidence of efficacy. Strong evidence also supports the use of antimalarial drugs in patients with lupus nephritis: Treatment with these agents is associated with reductions in disease activity and progression to chronic kidney disease.  In this study, most of the patients were started on a combination of corticosteroid and antimalarial, i.e., prednisolone and hydroxychloroquine with good clinical outcome.
| Conclusion|| |
It has been noted that the clinical manifestations can vary between fever, arthritis, and skin rash to severe systemic involvement. Most of the patients are females of childbearing age group. High suspicion is needed to diagnose the disease at its initial stages and autoantibody profiling should be done to support the diagnosis and to determine the prognosis. Antimalarials in combination with immunomodulatory drugs are the mainstay of treatment. Appropriate treatment should be initiated at the earliest to prevent the progression of the disease.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Hsieh SC, Yu CL. Autoantibody profiling in systemic lupus erythematosus. Curr Biomark Find 2013;3:55-65.
Binoy JP, Muhammed F, Kumar N, Razia MV. Clinical profile of systemic lupus erythematosus in North Kerala. J Indian Rheumatol Assoc 2003;11:94-7.
Osio-Salido E, Manapat-Reyes H. Epidemiology of systemic lupus erythematosus in Asia. Lupus 2010;19:1365-73.
Malaviya AN, Singh RR, Singh YN, Kapoor SK, Kumar A. Prevalence of systemic lupus erythematosus in India. Lupus 1993;2:115-8.
Lahita RG. The role of sex hormones in systemic lupus erythematosus. Curr Opin Rheumatol 1999;11:352-6.
Lee SJ, Silverman E, Bargman JM. The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nat Rev Nephrol 2011;7:718-29.
Kosaraju K, Shenoy S, Suchithra U. A cross-sectional hospital-based study of autoantibody profile and clinical manifestations of systemic lupus erythematosus in South Indian patients. Indian J Med Microbiol 2010;28:245-7.
Agrawal SR, Tiewsoh I, Rajput A, Jain A. A cross-sectional hospital based study of clinical and immunological profile of systemic lupus erythematosus patients from central rural India. Indian J Allergy Asthma Immunol 2013;27:33-7.
Saigal R, Kansal A, Mittal M, Singh Y, Maharia HR, Juneja M. Clinical profile of systemic lupus erythematosus patients at a tertiary care centre in Western India. J Indian Acad Clin Med 2011;13:27-32.
Santhanam S, Madeshwaran M, Tamilselvam TN, Rajeswari S. Clinical and immunological profile of SLE patients: Experience from a Chennai-based tertiary care centre (revisited). Internet J Rheumatol Clin Immunol 2016;4:OA1. DOI: 10.15305/ijrci/v4i1/145.
[Figure 1], [Figure 2]
[Table 1], [Table 2]