HLA class I and class II association with ankylosing spondylitis in a southern Indian population.

Ankylosing spondylitis (AS) is a chronic inflammatory condition associated with HLA B27. But the association is not absolute. Hence association with other HLA class I antigens and class II alleles was studied in a southern Indian population. Sixty-five patients with primary AS were typed serologically for HLA class I antigens. Age- and sex-matched disease controls (37 with enterogenic reactive arthritis [ReA] and 25 with undifferentiated spondyloarthropathy [UnSpA]) and 124 healthy controls were studied. PCR-based DNA-SSO typing for DQA1 and DQB1 was performed on 20 patients with AS and 38 healthy controls. Twenty-three patients with AS and 39 controls were typed for DRB1 alleles. HLA B27 was positive in 76.9 % of the cases of AS (RR 811), 59.5% of those with ReA (RR 9.3), and 40% of the patients with UnSpA (RR 9.3), while none of the controls were B27 positive. The P value for positive association was highly significant for B27 in all the three groups. B27 positivity was associated with earlier age of onset of disease in all the diseases compared to the B27-negative group. HLA Cw2 was positively associated with AS (P highly significant; OR 52) and ReA (P = 0.0003; OR 14.2). HLA A1 and CW6 were significantly negatively associated only with AS (P = 0.0001 and 0.00004 and OR 0.25 and 0.02, respectively). None of the HLA class II alleles were significantly associated with AS. The apparent association with DRB1*11 (P = 0.03) was lost after Yates correction.

IgM, IgG, and IgA response to enterobacteria in patients with ankylosing spondylitis in southern India.

IgM, IgA, and IgG response to three different antigenic preparations-lipopolysaccharide (LPS), culture supernatant proteins, and outer membrane protein (OMP) of Klebsiella pneumoniae, Escherichia coli and Salmonella typhi-were measured in the sera of 20 patients with primary ankylosing spondylitis (AS), 10 with enterogenic reactive arthritis (ReA) (disease controls), and 15 voluntary blood donors (healthy controls) by ELISA using biotinylated anti-human immunoglobulins M, G, and A. Serum immunoglobulin levels were measured by immunoturbidimetric assay in 20 AS patients, 20 patients with enterogenic reactive arthritis (ReA), 20 with ulcerative colitis (UC), and 20 voluntary blood donors. Student's t-test was applied for comparison. Compared to healthy controls, AS patients showed significantly elevated IgG response against culture supernatant proteins of all the three organisms (P <0.05), LPS of E. coli (P < 0.05) and Klebsiella (P < 0.005), as well as OMP only of Klebsiella pneumoniae. This was reflected as significantly elevated IgG level in AS compared to controls (P < 0.05 vs. ReA and 0.005 vs. UC and healthy controls). This suggests the involvement of outer membrane proteins of Klebsiella pneumoniae in the pathogenic mechanism of ankylosing spondylitis.

Class II MHC alleles in rheumatoid arthritis in Tamilnadu, India: is there an association?

Rheumatoid arthritis (RA) was reported to be associated with class II MHC alleles in different ethnic populations. A similar study was undertaken to determine the association of class II MHC with RA patients of Tamilnadu (Tamil-speaking Hindus), India. Thirty patients with RA and 39 healthy controls were included. Polymorphic second exons of the DRB1, DQA1, and DQB1 genes were amplified and subjected to SSOP typing. No allele was found to be significantly associated with RA. However DRB1*11 (P = 0.01) and DQB1*0302 (P = 0.02) were significantly associated with rheumatoid factor-positive RA patients. (All the DRB1*11-positive RA patients had either *04 or *10 allele as their second allele. This study is first of its kind in this population.

Pattern of rheumatic diseases in south India. IV. Clinical profile of juvenile rheumatoid arthritis.

An analysis of 100 consecutive cases of juvenile rheumatoid arthritis from South India revealed a male preponderance (62%), a lower incidence of the systemic onset variety (10%) and equal incidence of systemic features when compared with the West. Knees and ankles were the joints commonly involved. The incidence of elevated erythrocyte sedimentation rate and C reactive protein, with haemoglobin levels below 10 g/dl was highest in the systemic onset variety. The polyarticular and systemic onset group responded well to aspirin, while the pauciarticular group responded well to indomethacin.

Pattern of rheumatic diseases in south India. V. Ankylosing spondylitis. A clinical and radiological study.

One hundred and two patients from South India with primary ankylosing spondylitis (AS) were analysed clinically and radiologically. The mean age of onset was 26 years, with a male to female ratio of 16:1. Eleven patients presented as juvenile ankylosing spondylitis. The mode of presentation of AS included axial involvement in 59, peripheral arthritis in 38, heel pain in 18 and acute anterior uveitis (AAU) in 11. The overall incidence of extra axial features was high (90 patients). These included subjects with peripheral arthritis (49), heel pain (35), AAU (14), rib pain (11), aortic regurgitation (8), apical pulmonary fibrosis (5), mitral regurgitation (2) and conduction defects (2). Peripheral arthritis was characteristically asymmetrical and oligo articular, and involved lower limb joints. No renal involvement was noticed. Radiologically, bilateral sacroilitis was seen in 80% of cases.

Progressive systemic sclerosis in south India.

Seventy eight patients with progressive systemic sclerosis (PSS) were seen over a period of 14 years. They were analysed after clinical, haematological, biochemical, immunological and radiological investigations for comparison with other Indian and Western studies. Nine of the 78 were cases of childhood PSS. There was a female preponderance (3.9:1) and the peak age of occurrence was the 4th decade (32.1%). Arthralgia (53.8%) and skin thickening (70.5%) were the common presenting symptoms. Raynaud's phenomenon (28.2%) was less common. Involvement of the skin was present in all the patients and skin biopsy was positive in 96% of the cases. Joints were affected in 66.7%; internal organs were involved in 52.6%. Antinuclear antibody was positive in 56.8%. Abnormal echocardiography (37.6%) and barium studies (20.4%) were seen. Restrictive airway pattern by pulmonary function test was present in 55%. Death occurred in 5 patients, of whom 3 died of severe pulmonary hypertension.

Double blind, placebo controlled trial on the cytoprotective effect of misoprostol in subjects with rheumatoid arthritis, osteoarthritis and seronegative spondarthropathy on NSAIDs.

Ninety arthritic patients were randomly allotted to receive misoprostol 200 micrograms thrice daily or placebo, for 4 weeks, while they were started on various NSAIDs. While upper gastrointestinal symptoms occurred equally in both groups, patients on placebo had significantly more post-therapy abnormal endoscopy findings. Misoprostol was well tolerated without any adverse side effects; it did not interfere with the therapeutic efficacy of the NSAIDs. Arthritic patients requiring long term NSAID therapy appear to benefit from misoprostol because of its cytoprotective effect on the gastrointestinal mucosa.

Juvenile rheumatoid arthritis--Madras experience.

In a prospective study of 1,053 consecutive children who attended the Rheumatic Care Centre, Government General Hospital, Madras from 1991 to 1995, 331 children fulfilled the criteria proposed by the American Rheumatism Association as modified by Cassidy et al for the diagnosis of Juvenile Rheumatoid Arthritis. These children were thoroughly examined and investigated and classified into 3 onset types which was then sub-classified into early entry and late entry groups based on the duration of illness. Other arthritic conditions were excluded. There were 44 cases belonging to Systemic onset, 171 belonging to polyarticular onset and 116 belonging to oligoarticular onset type. In the systemic onset type 44/44 patients had fever, 40/44 had lymphadenopathy and 19/44 had skin rash; wrists and knees 31/44 were the most commonly involved joints; neck involvement was present in 13/44 of the cases; ANA was positive in 5/44 cases and anaemia was seen in 24/44 cases. In polyarticular onset type wrists 119/171, knees 143/171, hip joints 105/171 and ankles 113/171 were commonly involved; in the RF +ve subtype 3/23 had subcutaneous nodules and 7/23 were positive for ANA; in the Rf -ve subtype 59/148 were positive for ANA. In the oligoarticular subtype-1 ANA was positive in all cases but iridocyclitis was not seen in any case. In oligoarticular subtype-2 HLA B27 was positive in 13/26 cases while Sacroilitis was seen in 16/26 cases. In oligoarticular type-3 HLA B27 was negative.

Childhood systemic lupus erythematosus in south India.

Out of 330 adult Systemic Lupus Erythematosus (SLE) cases who attended the Rheumatic Care Centre, Government General Hospital, 59 children were analysed. There was no case with onset before the age of 5 years. There were 49 females and 110 males (M:F = 1:4.9). The initial manifestations were fever (67%), arthritis (61%), skin rash (59%) and lymphadenopathy (27.1%). There was no case of Raynaud's phenomenon. Only 10.1% of patients presented with thrombocytopenic purpura. In the cumulative clinical features, arthritis in 86.6%, fever in 79.8%, skin rash in 69.4%, lymphadenopathy in 61% and hepatosplenomegaly in 39.9% were observed. Renal involvement was seen in 49.1%, neuropsychiatric manifestations in 27.1%, pleuropulmonary in 22% and cardiac manifestations in 10.2%. Anaemia was seen in 50.8%, leukopenia in 18.4%, thrombocytopenia in 11.8%, ANA in 100%, anti-dsDNA in 92.3%, anti-Sm in 34.7%, anti-SSA in 38.5%, anti-SSB in 15.4%, ACL in 30.8%, low C3 in 50% and false positive VDRL in 3.3%. Death occurred in 8 children, 3 due to infection, 2 due to renal causes, 1 due to cardiac and 2 due to central nervous system involvement.

Effect of type II collagen treatment on the antioxidant status in immune tissues of adjuvant induced arthritic rats.

Adjuvant induced arthritis (AIA) is a model widely used to study Rheumatoid arthritis (RA). In the present study, lipid peroxides level in spleen and thymus of AIA rats was observed to be significantly high compared to normal rats. A significant decrease in ascorbic acid (ASA), reduced glutathione (GSH), superoxide dismutase activity (SOD) was also observed in spleen and thymus of AIA rats compared to normal rats. There was also a steady increase in the circulating immune complex level (CIC) throughout the experimental period in serum of AIA rats. In the present investigation, it was decided to study the effect of pre and post treatment with TYPE II collagen on the antioxidant status and the circulating immune complex level in AIA rats. The results from the present work indicates that the pretreatment with TYPE II collagen was effective in bringing significant changes on all the parameters studied in AIA rats. The post treatment with TYPE II collagen was effective in bringing significant changes on the CIC immune complex level and GSH content in the thymus tissue of AIA rats. The present work suggests that the pre treatment with TYPE II collagen was more effective in suppressing the disease than the post treatment.

Rheumatoid arthritis and connective tissue disorders: India and South-East Asia.

With a few exceptions, there remains a paucity of good epidemiological studies from India and South-East Asia. The overall impression is that the prevalence of rheumatoid arthritis (RA) is slightly less compared with the West and follows a milder course. There may be differences in the articular expression of the disease with the wrist and forefoot less commonly affected than in Caucasian studies. Extra-articular manifestations and erosive change are less frequent and severe. HLA DR4 does not correlate with seropositivity and severity of RA. The prevalence of SLE may be less in the Indian subcontinent than in the West. However, recent indications are that in South-East Asia and the Pacific region the prevalence morbidity and mortality are higher than in developed countries. An improvement in socio-economic conditions may be accompanied by an improvement in the survival of patients with SLE.

Systemic lupus erythematosus in India.

The first case of systemic lupus erythematosus (SLE) was reported from India in 1995 followed by two more case reports and further, a series of eight cases, till 1969. Since the establishment of a clinical immunology laboratory at a major teaching institution in New Delhi in 1968, SLE was extensively studied and reported from that centre. From mid-1980 onwards several other centres in different regions in India including Chennai (old name Madras), Mumbai (old name Bombay), Calcutta and Hydrabad, also published their regional experience on SLE. Based on these data, the present report describes the clinical and laboratory characteristics of 1366 SLE patients seen in different regions of India. Arthritis, rash, photosensitivity, seizures and psychosis were seen in comparable proportions to other racial groups. Similarly, ANA and anti-DNA antibody positivity was also within the range seen in other racial groups. When compared with other series, however, alopecia, renal lupus, oral ulcers and neurological involvement was seen in higher proportions, reaching statistically significant figures in comparison to some racial groups. In contrast, haematological manifestations were seen in significantly less proportions in comparison to some of the racial groups. Serositis and discoid lesions were also seen in lower proportions than in most of other races. The proportion of those with anti-Sm antibodies was in between two extremes of highest among Africans and Israelis and lowest among Chinese and Europeans. Other manifestations were comparable to most other racial groups. Compared to North American and European reports, significantly low 5 and 10 year survival was observed among patients from India. This could be related to the general public health situation in the country including less than optimal management facilities in hospitals, delay in diagnosis due to lack of awareness of the disease, referral bias where only serious patients reach major city hospitals, or a truly severe disease among Indians, or a combination of these genetic, environmental and/or sociocultural factors. The Main causes of death were irreversible renal damage, infections and neurological involvement. Despite a comparable prevalence of anticardiolipin antibodies (aCL) and lupus anticoagulants (LAC), clinical antiphospholipid syndrome was significantly less common. Genetic studies showed appreciable increase of HLA DR4 (37.5%) among patients compared with controls (18%). Additionally the haplotype B8-DR3 was encountered frequently in the patient group.