Tumor necrosis factor-alpha microsatellite polymorphism association with rheumatoid arthritis in Indian patients.

BACKGROUND: Level of TNF-alpha increases significantly in synovial fluid of rheumatoid arthritis (RA) patients. It is proposed that tumor necrosis factor (TNF) microsatellite alleles may influence its expression and presumably can contribute to the disease severity. However, there is a lack of such study to predict any such association with RA in an Indian population. METHODS: In this study, we investigated the differential pattern of distribution of TNF microsatellite alleles in an Indian population and its association with RA. One hundred eighteen RA patients and 120 healthy individuals were genotyped for TNF microsatellite alleles using Genescan. Odds ratio was calculated to demonstrate the correlation between allelic distribution and clinical severity. RESULTS: The study shows that distribution of TNF microsatellite alleles in an Indian population is very different from other Asian Oriental and Western populations, except for some similarities with an Italian population. Frequency of microsatellite TNFd3 allele (9.24 vs. 3.85%, chi(2)=5.6, p < or =0.0179, OR=0.393, 95% CI=0.177-0.87) and more interestingly TNFd3 containing haplotypes has been found significantly reduced in patients. On the contrary, TNFb5 allele frequency increased in the patients (22.3 vs. 30.8%, chi(2)=4.4, p < or =0.036, OR=1.55, 95% CI=1.027-2.344) as compared to controls. Furthermore, significant increase in frequency of this allele in severe patients (22.3 vs. 33.8%, chi(2)=6.22, p < or =0.013, OR=1.78, 95% CI=1.132-2.798) along with the significant increase in haplotypes containing this allele supports the association of TNFb5 with disease severity. CONCLUSIONS: In an Indian population, TNFb5 may be considered as a risk factor, whereas TNFd3, unlike others, may be protective for RA.

Anti-MBL autoantibodies in patients with rheumatoid arthritis: prevalence and clinical significance.

Occurrence of autoantibodies in patients' sera is the characteristic feature of autoimmune disorders. We assessed the presence of anti-mannose binding lectin (MBL) autoantibodies in the sera of 107 rheumatoid arthritis (RA) patients and 121 control subjects by enzyme immunoassay. Elevated levels of anti-MBL autoantibodies in the sera of RA patients (P<0.0001) was detected for the first time. The ratios of anti-MBL positive in RA patients and controls were respectively 60.7% and 1.65%. Experiments were then designed to understand the functional relevance of these autoantibodies. An inverse correlation of anti-MBL autoantibodies with serum MBL levels (P=0.001) and MBL complex activity (P=0.02) was observed without genetic association between MBL polymorphisms and anti-MBL autoantibody secretion. A significant increase (P=0.038) in the level of anti-MBL autoantibodies was observed in 23 synovial fluid samples in comparison to the serum samples. Moreover, the anti-MBL autoantibodies were found to be more often present in the sera of RA patients (60.75% sensitivity, 98.35% specificity and 0.913 area under the ROC curve) in comparison to the IgM and IgG isotypes of rheumatoid factors (RF). Anti-MBL autoantibodies were still positive in 25.23% RA patients when both the RF isotypes were negative. Also, in RA patients, at all stages of disease activity and joint deformity, anti-MBL autoantibodies were more often present than both the RF isotypes. Therefore, the significant presence of anti-MBL autoantibodies enunciates that anti-MBL autoantibodies might have a diagnostic value; however, more studies are needed to confirm the role of anti-MBL autoantibodies in the diagnosis of rheumatoid arthritis.