MHC haplotype and B cell autoimmunity: Correlation with pathogenic IgG autoantibody subclasses and Fc glycosylation patterns

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  • Larissa Nogueira Almeida
    Institute for Systemic Inflammation Research University of Lübeck Lübeck Germany
  • Ann‐Katrin Clauder
    Institute for Systemic Inflammation Research University of Lübeck Lübeck Germany
  • Lingzhang Meng
    Center for Systemic Inflammation Research (CSIR), School of Preclinical Medicine Youjiang Medical University for Nationalities Baise City (Bose), Guangxi Zhuang Autonomous Region China
  • Marc Ehlers
    Laboratories of Immunology and Antibody Glycan Analysis, Institute for Nutritional Medicine University of Lübeck and University Medical Center Schleswig‐Holstein Lübeck Germany
  • Sergio Arce
    Department of Biomedical Sciences University of South Carolina School of Medicine‐Greenville Greenville SC USA
  • Rudolf Armin Manz
    Institute for Systemic Inflammation Research University of Lübeck Lübeck Germany

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<jats:title>Abstract</jats:title><jats:p>Genome‐wide association studies (GWAS) have identified many genes that are associated with the development of certain autoimmune disorders, but the MHC haplotypes still represent the most prevalent genetic risk factor for many autoimmune diseases. The mechanisms by which MHC‐associated genetic susceptibility translates into B cell autoimmunity and the development of autoimmune diseases are complex. There is increasing evidence that the MHC haplotype modulates autoreactive B cell responses in multiple ways. Instead of merely inhibiting the production of IgG autoantibodies and mediating complete immunological tolerance, the non‐permitting MHC haplotypes seem to facilitate the production of IgG autoantibodies exhibiting Fc glycosylation patterns that are associated with reduced pathogenicity and a protective cytokine profile of T follicular helper (Tfh) cells. Here, we discuss mechanisms linking MHC haplotypes to the production of pathogenic IgG autoantibodies, which could be relevant for the development of improved diagnosis, particularly in the context of individual medicine.</jats:p>

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