A study of prevalence of autoantibodies in patients with lichen planus from Mumbai, India

Background: Lichen planus is a common chronically relapsing autoimmune skin condition with poorly understood etiology. Apart from cellular immunity, presence of various antibodies has been hypothesized. Various studies have found the presence of serum anti-nuclear antibody, anti-mitochondrial antibody, anti-desmoglein 1 and 3 antibodies, anti-keratinocyte antibody and anti-thyroglobulin antibody in patients of cutaneous and oral lichen planus. Aim: To study the prevalence of autoantibodies and the clinical spectrum of disease in an Indian patient subpopulation with lichen planus. Methods: A cross-sectional epidemiological study comprising 100 lichen planus patients was conducted in the dermatology outpatient department of Seth G.S Medical College and King Edward Memorial Hospital, Mumbai, Maharashtra, India. Serum concentrations of circulating anti-nuclear antibodies, anti-desmoglein 1 antibody, anti-desmoglein 3 antibody, anti-keratinocyte antibodies, anti-mitochondrial antibodies and anti-thyroglobulin antibodies were determined by indirect immunofluorescence. Pairs of groups were compared using “Student's t-test” for normally distributed continuous data. The “χ2-test” was used for the categorical variables as needed. Statistical significance was set at P < 0.05. Results: It was found that 65 (65%) patients showed the presence of at least one of the six autoantibodies that we studied, while 35 (35%) tested negative for all six of them. Positivity of anti-keratinocyte antibody in 26 (26%), anti-nuclear antibody in 22 (22%), anti-desmoglein 1 antibody in 19 (19%), anti-desmoglein 3 antibody in 16 (16%), anti-mitochondrial antibody in 9 (9%) and anti-thyroglobulin antibody in 6 (6%) patients was detected. It was observed that 55 (71.4%) patients of cutaneous lichen planus, 6 (46.1%) patients of mucosal lichen planus and 4 (40%) patients of cutaneous and mucosal lichen planus overlap showed presence of at least one autoantibody. Conclusion: This study provides the serological parameters of a population of lichen planus from western India. Presence of autoantibodies in lichen planus suggests the possible role of humoral immunity in lichen planus. Identifying antibodies linked to lichen planus may help in identifying suitable diagnostic tests and therapeutic targets. Well-controlled studies with larger sample size are the need of the hour to confirm the role of humoral immunity in lichen planus. Limitations: Studies with a larger number of patients as well as controls should be undertaken to further evaluate the role of autoantibodies in lichen planus.

Mannose binding lectin (MBL) 2 gene polymorphism & its association with clinical manifestations in systemic lupus erythematosus (SLE) patients from western India.

Background & objectives: systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies. Mannose binding lectin (MBL) is an important element of the innate defense system. the present study was undertaken to determine whether variant alleles in MBL2 gene were associated with disease severity in SLE patients. Methods: The MBL alleles [-550, -221, +4, Codon 52, Codon 54 and Codon 57] were studied by PCR- RFLP (restriction fragment length polymorphism) method in 100 SLE patients fulfilling ACR (American College of Rheumatology) criteria along with 100 healthy controls. SLE disease activity was evaluated using SLE Disease Activity Index (SLEDAI) score. Results: Homozygosity for MBL variant allele (O/O) was observed in 24 per cent of the SLE patients compared to 16 per cent of the normal controls, while no difference was found for heterozygosity (A/O) (37 vs 35%). A significant difference was reported in incidence of double heterozygosity for mutant allele B and D (B/D) among SLE patients as against control group (p = 0.015). MBL genotypes did not show any association with renal involvement. Interpretation & conclusions: In this study from western India, MBL gene polymorphism showed an influence as a possible risk factor for susceptibility to SLE, but had no direct effect on disease characteristics. Further studies need to be done on a larger number of SLE patients in different regions of the country.

Fc γ R IIB gene polymorphisms in Indian systemic lupus erythematosus (SLE) patients.

Background & objectives: Receptors for the Fc fragment of immunoglobulin G (Fc γ Rs) represent the link between humoral and cellular immune responses. Polymorphisms in Fc γ Rs have been identified as genetic factors influencing susceptibility to various autoimmune diseases. This study was aimed to identify Fc γ R IIB genotypes in Indian systemic lupus erythematosus (SLE) patients and to correlate these with clinical presentation and autoantibody profile. Methods: Eighty consecutive clinically diagnosed SLE patients were included. SLE patients were classified according to the American College of Rheumatology (ACR) criteria. Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). PCR-RFLP method was used to detect Fc γ R IIB polymorphism. Results: Of the 80 SLE patients, 53 were LN and 27 were SLE without nephritis. The mean SLEDAI score at evaluation was 6.5 ± 5.8. Among SLE patients Fc γ R IIB genotype frequency was 61.2 per cent for Ile/Thr, 20.0 per cent for Thr/Thr and 18.8 per cent for Ile/Ile as compared to 65, 12.5 and 22.5 per cent respectively among normal population. There was no significant difference for Fc γ R IIB genotypes between SLE and normals. The allele frequency for Thr allele in SLE patients was slightly higher (0.51) than in normals (0.45). Thr allele frequency in LN patients was slightly higher (0.53) than in SLE patients without nephritis (0.49). Though a higher percentages of symptoms like renal manifestations (81.3%), arthritis (62.5%) and oral ulcer (56.3%) were noted in patients with Thr/Thr genotypes, no significant difference was noted when these patients were compared with Ile/Ile and Ile/Thr genotypes. Interpretation & conclusions: The findings of this study indicate towards an involvement of Thr allele with SLE disease severity and clinical presentation in Indian SLE patients. Future study on a large sample is needed to support this finding to understand the association of Fc γ R IIB 232Thr/Thr genotype as a susceptibility factor in SLE.

Anti-nucleosome antibodies as a disease marker in systemic lupus erythematosus and its correlation with disease activity and other autoantibodies.

Background: Detection of anti-nucleosome antibodies (anti-nuc) in patients with systemic lupus erythematosus (SLE) has been well established and it is claimed that their presence is associated with disease activity. Aims: The aim of this study is to evaluate the incidence of anti-nuc antibodies and to correlate them with disease activity and its association with other autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), as well as autoantibodies to histone subfractions like H1, (H2A-H4) complex, H2B, and H3. Methods: This cross-sectional study included 100 SLE patients referred from the Rheumatology, Dermatology, and Nephrology Departments. SLE disease activity was evaluated by using SLE-Disease Activity Index (SLEDAI) score. A patient was defined as having active SLE when the SLEDAI score was more than 5.0. Fifty normal controls were also tested as a healthy control group. Anti-nuc antibodies, anti-dsDNA, and AHA were tested by Enzyme-Linked Immunosorbent Assay (ELISA) and ANA was detected by an indirect immunofluorescence test. Results: All patients studied were in an active stage of disease and were untreated, of which 44 patients had renal biopsy-proven kidney involvement, which was categorized as lupus nephritis (LN) and 56 patients did not show any renal manifestations (SLE without LN). Anti-nuc antibodies were positive in 88%, anti-dsDNA in 80%, and AHA in 38% of the cases. ANA was positive in all SLE patients studied. None of the normal controls was found to be positive for these antibodies. Although a slightly higher incidence of autoantibodies were noted in LN, there was no statistical difference noted between LN and SLE without LN groups for anti-nuc and anti-dsDNA antibodies (p > 0.05). A higher incidence of autoantibodies to ANA specificities were noted in anti-nuc positive cases, but there was no statistical difference between anti-nuc positive and anti-nuc negative cases for ANA specificities among LN and SLE without nephritis groups (p > 0.05). Conclusions: Anti-nuc antibody detection could be a better tool for the diagnosis of SLE. Although there was no significant difference in LN and SLE without LN groups, this study suggests that anti-nuc detection can be useful as an additional disease activity marker to other laboratory tests.

APO-1/Fas gene: Structural and functional characteristics in systemic lupus erythematosus and other autoimmune diseases.

Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. It is characterized by the presence of autoantibodies reactive against various self-antigens. Susceptibility to SLE is found to be associated with many major histocompatibility complex (MHC) and non-MHC genes, one of which is APO-1/Fas gene, which is present on chromosome 10 in humans. The APO-1/Fas promoter contains consensus sequences for binding of several transcription factors that affect the intensity of Fas expression in cells. The mutations in the APO-1/Fas promoter are associated with risk and severity in various autoimmune diseases and other malignancies. The APO-1/Fas receptor is expressed by many cell types. Two forms of APO-1/Fas protein that are involved in regulation of apoptosis have been identified. Fas receptor-mediated apoptosis plays a physiological and pathological role in killing of infected cell targets. In this review, we have focused on APO-1/Fas gene structure, promoter variants and its association with SLE and other autoimmune diseases. Functional aspects of Fas receptor in apoptosis are also discussed.

Fc gamma receptor polymorphisms in systemic lupus erythematosus and their correlation with the clinical severity of the disease.

Receptors for the Fc domains of IgG (Fc γ R) play a critical role in linking humoral and cellular immune responses. The various Fc γ R genes may contribute to differences in infectious and immune related diseases in various ethnic populations. Polymorphisms of Fc γ R mainly Fc γ R IIA, IIB, IIIA, IIIB have been identified as genetic factors influencing susceptibility to disease or disease course of a prototype autoimmune disease like Systemic Lupus Erythematosus (SLE). Activated and inhibitory Fc γ Rs seem to play an important role in the pathogenesis of SLE, in initiation of autoimmunity, the subsequent development of inflammatory lesions and finally immune clearance mechanisms. This review focuses on the role of Fc γ R polymorphism and their association with clinical manifestations and initiation of autoantibody production, inflammatory handling of immune complexes and disease development in SLE patients.

Hematological profile of HIV positive patients.

A series of 500 HIV positive patients referred to our centre for CD4 and CD8 cell enumeration are included in this study. The following parameters were studied in each of these patients: Hb, RBC indicates, WBC count, platelet count, three part differential count, absolute CD4 and CD8 counts. Male:Female ratio of 4.9:1 was noted 30.8% patients has anemia (Hb<10 gm%), with an average Hb value of 8.1 gm%. The anemia was normochromic, normocytic in 61% of patients, microcytic in 33% and macrocytic in 6% patients. The absolute CD4 count was less than 200 ul in 50.2% patients with an average value of 92/ul. Thrombocytopenia was seen in 13% patients with average platelet count 0.92x10(3)/ul.