Abstract
IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. It has only recently been appreciated, that members of this group share relevant immunobiological and therapeutic aspects even though different antigens, tissues and organs are affected: glomerulonephritis (kidney), pemphigus vulgaris (skin), thrombotic thrombocytopenic purpura (hematologic system) muscle-specific kinase (MuSK) in myasthenia gravis (peripheral nervous system) and autoimmune encephalitis (central nervous system) to give some examples. In all these diseases, patients’ IgG4 subclass autoantibodies block protein-protein interactions instead of causing complement mediated tissue injury, patients respond favorably to rituximab and share a genetic predisposition: at least five HLA class II genes have been reported in individual studies to be associated with several different IgG4-AID. This suggests a role for the HLA class II region and specifically the DRβ1 chain for aberrant priming of autoreactive T-cells toward a chronic immune response skewed toward the production of IgG4 subclass autoantibodies. The aim of this review is to provide an update on findings arguing for a common pathogenic mechanism in IgG4-AID in general and to provide hypotheses about the role of distinct HLA haplotypes, T-cells and cytokines in IgG4-AID.
Highlights
TO IGG4-AIDIgG4 autoimmune diseases (IgG4-AID) are a group of autoimmune diseases that are mediated by antigen-specific autoantibodies of the IgG4 subclass [1, 2]
Alleles of the DRB1 and DQB1 genes were associated with most IgG4 autoimmune diseases, suggesting that the HLA class II genes play a role in typical autoimmune diseases, and in the induction of an IgG4 specific autoimmune response
Two risk alleles for membranous nephropathy with PLA2R antibodies were identified in a Han Chinese population in DRB1*15:01 and DRB1*03:01 [43], either of which were found in 73.6% of the patient cohort, and that contained specific amino acid variants in the peptide-binding groove of the HLA class II molecules which is responsible for antigen presentation to the T-cell receptor [43, 44]
Summary
TO IGG4-AIDIgG4 autoimmune diseases (IgG4-AID) are a group of autoimmune diseases that are mediated by antigen-specific autoantibodies of the IgG4 subclass [1, 2]. Alleles of the DRB1 and DQB1 genes were associated with most IgG4 autoimmune diseases, suggesting that the HLA class II genes play a role in typical autoimmune diseases, and in the induction of an IgG4 specific autoimmune response.
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