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.
Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
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.
Study site: SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
An analysis of the clinical and serological features of 12 male and 122 female patients with SLE was done to determine whether sex related differences exist. We found a lower incidence of mucocutaneous symptoms and arthritis but an increased incidence of discoid lesions, pleuritis and pericarditis in males at disease onset. During the disease course, there was a lower incidence of arthritis, a similar prevalence of mucocutaneous symptoms but an increased incidence of pleuritis in males with a trend towards renal involvement. These findings were however not statistically significant except for the higher incidence of thrombosis among males. Serologically, both groups showed similar frequencies of autoantibodies and hypocomplementaemia. Although the study was small, it was shown that several sex-related differences in the clinical and serological features exist in Malaysian SLE patients.
Study site: SLE Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
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