BACKGROUND: Studies have shown that certain genes within the major histocompatibility complex predispose to systemic lupus erythematosus (SLE) and may influence clinical and autoantibody expression. Thus, we studied the frequency of HLA-DR, -DQA, -DQB and -DPB alleles in ethnic Malays with SLE to determine the role of these genes in determining disease susceptibility and their association with clinical and immunological manifestations.
METHODS: Fifty-six Malay SLE patients were enrolled into the study. Demographic, clinical and immunological findings were obtained from medical records. HLA-DR, DQ and DP typing were done using modified PCR-RELP. Controls were from ethnically-matched healthy individuals.
RESULTS: We found a strongly significant association of the DR2 and DQB1 *0501 and DQB1*0601 (pcorr = 0.03, rr = 3.83, pcorr = 0.0036, rr = 4.56 and pcorr = 0.0048 and rr = 6.0, respectively). There was also a weak increase of DQB1*0.201 and DPB1*0.0901 with a weak decrease of DQA1*0601 and DQB1*0503 and *0301 which were not significant after corrections for multiple comparisons were made. There was a significant positive association of DR2 and DQB1*0501 with renal involvement and DR8 with alopecia. A nonsignificant increase of DQB1*0503 in patients with photosensitivity was noted. Significant autoantibody associations were also found: DQB1*0601 with anti-Sm/RNP, DR2 with antiSSA (Ro)/SSB (La), and DR2, DQB1*0501 and *0601 with antibodies to ds DNA. There was no specific DR, DQ or DP associations with age of disease onset (below 30 years or those at or above 30 years).
CONCLUSION: Our data suggests the role of the HLA class II genes in conferring SLE susceptibility and in clinical and autoantibody expression.
Study site: SLE Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
One hundred and seventy patients with systemic lupus erythematosus (SLE) were studied for the prevalence of antibodies to the small RNA-associated proteins Ro/SSA, La/SSB, Sm, U1RNP and Sm. The relationship of these autoantibodies to different races, sexes and clinical manifestations of SLE was evaluated. Passive immunodiffusion was employed using human spleen extract as antigen source for Ro and rabbit thymus extract for La, Sm and U1RNP. We found the prevalence of antibodies to be as follows: anti-Ro/SSA, 36%; anti-La/SSB, 8%; anti-Sm, 15% ; anti-U1RNP, 21%. Except for a low prevalence of anti-La, the prevalence of these antibodies was similar to that in Western studies, The prevalence of anti-Ro/SSA is similar to that reported in the Western studies, but lower than that reported in the Oriental patients from Singapore and Hong Kong. Linkages of anti-Ro with anti-La antibodies were usual; however, although anti-Sm antibodies were usually associated with anti-U1RNP, they were more frequently associated with anti-Ro antibodies. The Malay patients had a high prevalence of anti U1RNP compared to other races. No gender difference was detected. Anti-Sm antibody was associated with serositis and anti-U1RNP antibodies with Raynaud's phenomenon. No association was found between the presence of skin renal or cerebral manifestations and any specific antibodies or combination of antibodies.