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