HLA Antigens in Malay Patients with Systemic Lupus Erythematosus : Association with Clinical and Autoantibody Expression

Abstract

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

HLA-A*11 and novel associations in Malays and Chinese with systemic lupus erythematosus

“…In addition, we found that DRB4*0101101, 0102, 0103, DQB1*05, DRB1*1301-22, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 alleles were significantly increased. This different from a previous study which showed an increase in the DRB1*0501 and *0601 alleles only [10].…”

“…In the Japanese and Korean studies, the most common DRB1 allele was *1501 [17]. The increase of DR2 allele frequency in the Malay patient groups has been previously reported [10]. In contrast, no association was found between DR2 allele frequencies and SLE in the Malay patient group in this present study.…”

“…The only three previous publications on HLA associations in Malay [9,10] and Chinese [11] Malaysian SLE patients examined a small number of HLA loci. His study was aimed at examining a fuller set of HLA loci associations in a population of Malay and Chinese SLE patients.…”

Association of HLA-DQB1∗06 with susceptibility to systemic lupus erythematosus in Egyptians

“…Rezaieyazdi et al [10] also reported absence of significant association between DQ6 and severity of disease in their patients. Contrary to our results Malaysians demonstrated significant association of DQB1*0601 with anti-Sm/RNP and with anti-dsDNA [30]. Tunisians showed no significant association of HLA-DQB1*06 with any of the specific antibodies in SLE [21].…”

Autoimmune Studies and HLA Associations in SLE Patients from Mumbai

“…Recently a significant association and increased evidence of direct involvement in the pathogenesis of tissue injury by the anti SS-A/ Ro and SS-B/ La antibodies are reported (Mavragani et al 2000). In SLE multiple loci within the MHC have been implicated in susceptibility like HLA class II alleles, Complement components and TNF loci (Naves et al 1998;Gladman et al 1999;Galeazzi et al 2000;Huang et al 2001;Azizah et al 2001;Shankarkumar et al 2003). HLA DQ1 and DQ2 are also found to be associated with Ro, La, Sm and dsDNA autoantibodies.…”