Immune mechanisms of fibrosis and inflammation in IgG4-related disease. Issue 2 (March 2020)

• Record Type: Journal Article
• Authors: Pillai, Shiv; Perugino, Cory; Kaneko, Naoki
• Is Part Of: Current opinion in rheumatology. Volume 32:Issue 2(2020:Mar.)
• Publication Date: 2020-03
• Subjects: B cells -- cytotoxic CD4+T cells -- fibrosis -- IgG4-related disease; Rheumatology -- Periodicals; Arthritis -- Periodicals; Review Literature -- Periodicals; Rheumatic Diseases -- Periodicals; 616.723
• DOI: 10.1097/BOR.0000000000000686
• Languages: English
• ISSNs: 1040-8711

Abstract

Abstract : Purpose of review: To summarize recent advances in the understanding of the pathogenesis of IgG4-related disease. Recent findings: Limited 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. Summary: In 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.