Projects per year
The major histocompatibility complex haplotype represents the most prevalent genetic risk factor for the development of autoimmune diseases. However, the mechanisms by which major histocompatibility complex–associated genetic susceptibility translates into autoimmune disease are not fully understood. Epidermolysis bullosa acquisita is an autoimmune skin-blistering disease driven by autoantibodies to type VII collagen. Here, we investigated autoantigen-specific plasma cells, CD4+ T cells, and IgG fraction crystallizable glycosylation in murine epidermolysis bullosa acquisita in congenic mouse strains with the disease-permitting H2s or disease-nonpermitting H2b major histocompatibility complex II haplotypes. Mice with an H2s haplotype showed increased numbers of autoreactive CD4+ T cells and elevated IL-21 and IFN-γ production, associated with a higher frequency of IgG autoantibodies with an agalactosylated, proinflammatory N-glycan moiety. Mechanistically, we show that the altered antibody glycosylation leads to increased ROS release from neutrophils, the main drivers of autoimmune inflammation in this model. These results indicate that major histocompatibility complex II–associated susceptibility to autoimmune diseases acuminates in a proinflammatory IgG fraction crystallizable N-glycosylation pattern and provide a mechanistic link to increased ROS release by neutrophils.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
FingerprintDive into the research topics of 'IgG Fc N-Glycosylation Translates MHCII Haplotype into Autoimmune Skin Disease'. Together they form a unique fingerprint.
- 1 Finished
Potential and mutual interference of differently N-glycosylated murine and humane IgG and IgA subclass antibodies during IgG-mediated anaphylaxis
01.01.18 → 31.12.22
Project: DFG Projects › DFG Individual Projects