Association of the tumor necrosis factor alpha gene polymorphism with susceptibility and clinical-immunological findings of systemic lupus erythematosus.

The etiology of systemic lupus erythematosus (SLE) is unknown but genetic factors seem to play a role in the disease pathogenesis. The tumor necrosis factor alpha (TNFa) gene, encoded at the TNF locus in the MHC class III region, is now known to be an important candidate gene in SLE, due to the proinflammatory activities of the TNFa. The objectives of this study were to examine the role of the TNFa polymorphism for the susceptibility of Malaysian Chinese lupus patients to SLE and to determine its association with organ involvement. The allelic frequencies of the TNFa polymorphic variant (TNF2) of seventy lupus patients were determined during follow-up at the Medical Clinic of the National University Hospital Malaysia by PCR-RFLP technique. Sixty-four females and 6 males with a mean age of 33+/-12 years were included. Clinical data were obtained from case records. Autoantibody levels were measured by ELISA. Fifty-nine ethnically-matched blood donors were used as controls. The allelic frequency of the TNF2 variant was found to be significantly increased in the patients compared to the controls (52.8% vs 33.8%). SLE patients with the polymorphic TNF2 variant were found to be at increased risk of central nervous system involvement (p = 0.004, RR = 2.59) and to have an increased frequency of anti-La antibodies (p = 0.03). In view of these findings we suggest that TNF2 variant is playing a role in conferring susceptibility to SLE and in the disease pathogenesis.

The association of the HLA class II antigens with clinical and autoantibody expression in Malaysian Chinese patients with systemic lupus erythematosus.

The frequency of the HLA class II antigens/alleles (HLA-DR, DQ and DP) were studied in 70 Malaysian Chinese patients with systemic lupus erythematosus (SLE) to examine the contribution of these genes to disease susceptibility, their clinical expression and Immunological responses. This was done using modified PCR-RFLP technique. These samples were then compared with 66 ethnically matched controls. We found a strong association of the DQA1*0102 (p corr = 0.032, rr = 3.39), DQB1*0501 (p corr = 0.003, rr = 4.55), *0601 (p corr = 0.006, rr = 4.22) and DPB1* 0901(p corr = 0.02, rr = 4.58) with SLE. Clinically, we found a strong association of DR2 and DQA1*0301 with renal involvement and DQA1*0102 with alopecia. Immunologically, statistical analysis (Chi-square test ) showed a strong association of DQA1*0102 with anti-Ro/La antibodies while DQA1*0301 was observed to be strongly associated with antibodies to ds DNA. DQA1*0102 was found more frequently in those with a later disease onset (30 years of age or above). From these data we suggest that the HLA class II genes play a role in conferring disease susceptibility and clinical and immunological expression.