Inga Koneczny, Austria
Medical University of Vienna Institute of NeurologyPresenter of 2 Presentations
DISTINCT ALLELES OF THE HLA-DRB1/DQB1 GENE LOCI ARE ASSOCIATED WITH CLASS I IGG4 AUTOIMMUNE DISEASES: A SYSTEMATIC REVIEW AND META-ANALYSIS
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.
UPDATE ON IGg4 AUTOIMMUNE DISEASES
Abstract
Background and Aims
IgG4 autoimmune diseases are characterized by the presence of antigen-specific autoantibodies of IgG4 subclass, and contain well-characterised diseases such as MuSK myasthenia gravis, pemphigus and thrombotic thrombocytopenic purpura. Recently several new diseases were identified, and by now at least 21 antigens associated with IgG4 subclass are known. The IgG4 subclass is considered as immunologically inert and functionally monovalent The pathogenicity of IgG4 autoantibodies can be validated using our recently published classification system.
Methods
Using literature research, autoimmune diseases associated with IgG4 autoantibodies were identified. Clinical and immunological research data of identified diseases were critically reflected and the pathogenicity of the IgG4 autoantibodies was analysed using the classification system for IgG4 autoantibodies.
Results
As a result, one new class II and six new class III IgG4 autoimmune diseases were identified. New research data allowed a re-classification of Neurofascin-155 antibody associated CIDP as class I IgG4 autoimmune disease. IgG4 autoimmune diseases were found to be restricted to four distinct organs: 1) the central and peripheral nervous system, 2) the kidney, 3) the skin and mucous membranes and 4) the vascular system or soluble antigens in the blood circulation.
Conclusions
In conclusion, there are to date six class I (verified), five class II (likely) and ten class III IgG4 autoimmune diseases, of which five are class IIIa, with insufficient data and five class IIIb, which support pathogenic entities other than IgG4. The pathogenicity of IgG4 in IgG4 autoimmune diseases is associated with blocking of enzymatic activity or protein-protein interaction of their target antigen