Value of HLA-DR genotype in systemic lupus erythematosus and lupus nephritis: a meta-analysis

Abstract

Aim: Human leukocyte antigen (HLA)-DRB1 allele polymorphisms have been reported to be associated with systemic lupus erythematosus (SLE) susceptibility, but the results of these previous studies have been inconsistent. The purpose of the present study was to systematically summarize and explore whether specific HLA-DRB1 alleles confer susceptibility or resistance to SLE and lupus nephritis.

Methods: This review was guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach. A comprehensive search was made for articles from PubMed, Medline, Elsevier Science, Springer Link and Cochrane Library database. A total of 25 case-control studies on the relationship between gene polymorphism of HLA-DRB l and SLE were performed and data were analyzed and processed using Review Manager 5.2 and Stata 11.0.

Results: At the allelic level, HLA-DR4, DR11 and DR14 were identified as protective factors for SLE (0.79 [0.69,0.91], P < 0.001; 0.72 [0.60, 0.85], P < 0.0001; 0.47 [0.59, 0.95], P < 0.05, respectively). HLA-DR3, DR9, DR15 were potent risk factors for SLE (1.88 [1.58, 2.23], P < 0.001; 1.24 [1.07, 1.45], P < 0.05; 1.25 [1.10, 1.43], P < 0.001, respectively). However, HLA-DR8 was not statistically significant between the SLE group and control group (OR, 1.11 [0.96, 1.30], P > 0.05). DR4 and 11 (OR, 0.55 [0.39, 0.79], P < 0.01; 0.60 [0.37, 0.96], P < 0.05, respectively) conferred a significant protective effect for lupus nephritis. DR3 and DR15 (OR, 2.00 [1.49, 2.70], P < 0.05; 1.60 [1.21, 2.12], P < 0.001, respectively) were at a high risk of developing lupus nephritis. HLA-DR8, DR9 and DR14 (OR, 1.47 [0.9, 2.33], P > 0.05; 0.90 [0.64, 1.27], P > 0.05; 0.61 [0.36, 1.03], P > 0.05, respectively) were not statistically significant between the lupus nephritis and control groups.

Conclusions: The HLA-DR4, DR11, DR14 alleles might be protective factors for SLE and HLA-DR3, DR9, DR15 were potent risk factors. In addition, HLA-DR4 and DR11 alleles might be protective factors for lupus nephritis and DR3 and DR15 suggest a risk role. These results proved that HLA-DR3, DR15, DR4 and DR11 might be identified as predictors for lupus nephritis and SLE.

Keywords: lupus nephritis; meta-analysis; susceptibility; systemic lupus erythematosus.