A systematic review and meta-analysis of HLA class II associations in patients with IgG4 autoimmunity

Abstract

AbstractAutoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly inHLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case–control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies ofHLA-DQB1*05(G: OR 3.8; 95% CI 2.44–5.9;p < 0.00001; A: OR 2.54; 95% CI 1.82–3.55;p < 0.00001) andHLA-DRB1*14(G: OR 4.31; 95% CI 2.82–6.59;p < 0.00001; A: OR 4.78; 95% CI 3.52–6.49;p < 0.00001) and theHLA-DRB1*14-DQB1*05haplotype (OR 6.3; 95% CI 3.28–12.09;p < 0.00001/OR 4.98; 95% CI 3.8–6.53;p < 0.00001) were increased whileHLA-DRB1*13(G: OR 0.48; 95% CI 0.34–0.68;p < 0.0001; A: OR 0.46; 95% CI 0.34–0.62;p < 0.00001) was decreased in IgG4-AID patients. In conclusion, theHLA-DQB1*05,HLA-DRB1*14alleles and theHLA-DQB1*05-DRB1*14haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and theHLA-DRB1*13allele may protect from IgG4 autoimmunity.