Purpose of reviewTo summarize recent advances in the understanding of the pathogenesis of IgG4-related disease.Recent findingsLimited data exist to explain genetic susceptibility to IgG4-related disease and the underlying triggers for this disease have not yet been identified. Cytotoxic CD4+ T cells and activated B cells infiltrate affected organs and express proinflammatory and profibrotic molecules. Antigen presented by activated B cells likely reactivates cytotoxic CD4+ T cells in disease tissues and these T cells in turn induce the targeted apoptotic death of host cells in certain organs-which presumably present the same antigenic peptide on human leukocyte antigen class II molecules of relevance that was also presented on B cells during reactivation. A subsequent exaggerated tissue remodeling process is orchestrated by cytokines, chemokines, and enzymes secreted by both activated B cells and CD4+CTLs. These molecules induce an overexuberant repair process resulting in fibrosis and loss of target organ function.SummaryIn IgG4-related disease, presumably self-reactive cytotoxic CD4+ T cells infiltrate tissues, are reactivated by T cells and induce apoptotic death. Molecules secreted by activated B cells and by CD4+CTLs drive an exaggerated wound healing response resulting in fibrosis and compromised tissue function.
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