DISTINCT ALLELES OF THE HLA-DRB1/DQB1 GENE LOCI ARE ASSOCIATED WITH CLASS I IGG4 AUTOIMMUNE DISEASES: A SYSTEMATIC REVIEW AND META-ANALYSIS
- Inga Koneczny, Austria
Abstract
Background and Aims
IgG4 autoimmune diseases are an emerging group of severe autoimmune diseases such as MuSK Myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. They are caused by IgG4 autoantibodies that are pathogenic by a direct blocking mechanism. The aetiology of IgG4 autoimmunity is not known. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known to contribute to a genetic susceptibility to develop autoimmune diseases. We hypothesized that IgG4 autoimmune diseases (IgG4-AID) collectively may also share genetic associations with the HLA gene locus.
Methods
To address this possibility, we conducted a systematic review to identify case-control studies on class I IgG4 autoimmune diseases based on the HuGENet guidelines for genetic association studies and MOOSE guidelines on Meta-analysis Of Observational Studies in Epidemiology.
Results
We identified an increased frequency of HLA-DRB1*14 (genotype frequency: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; allele frequency: OR 4.78; 95% CI 3.52-6.49; p <0.00001) and HLA-DQB1*05 (genotype frequency: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; allele frequency: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (n: OR 6.3; 95% CI 3.28-12.09; p < 0.00001, 2n: OR 4.98; 95% CI 3.8-6.53; p < 0.00001), and a decreased frequency of HLA-DRB1*13 (genotype frequency: OR 0.48; 95% CI 0.34-0.68; p <0.0001; allele frequency: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) in patients with IgG4-autoimmune diseases.
Conclusions
The HLA-DRB1*14 and DQB1*05 allele may contribute as genetic risk factors to the susceptibility to develop IgG4 autoimmune disease, while HLA-DRB1*13 may have a protective effect.