Immunoglobulin G4+ clones identified by next-generation sequencing dominate the B cell receptor repertoire in immunoglobulin G4 associated cholangitis

• DOI: 10.1002/hep.26232
• Publication Date: 2013-01-09T05:57:42Z
• Authors: Lucas J. Maillett...; Marieke E. Dooren...; Paul L. Klarenbeek; Joanne Verheij; Frank Baas; Ronald P. Oude El...; Paul P. Tak; Niek de Vries; Ulrich Beuers
• Keywords: Antibody Repertoire

Abstract Immunoglobulin G4 (IgG4)-associated cholangitis (IAC) is a manifestation of the recently discovered idiopathic IgG4-related disease. The majority patients have elevated serum IgG4 levels and/or IgG4-positive B-cell and plasma cell infiltrates in affected tissue. We hypothesized that clonally expanded, class-switched B cells could be causal to these poorly understood phenomena. In prospective cohort six consecutive IAC patients, healthy controls, disease we used novel next-generation sequencing approach screen receptor (BCR) repertoires, blood as well tissue, for IgG4+ clones. A full repertoire analysis BCR heavy chain was performed using GS-FLX/454 customized bioinformatics algorithms (>10,000 sequences/sample; clones with frequency ≥0.5% were considered dominant). found most dominant within IgG+ BCRheavy peripheral at baseline only patients. all but none among 10 any immunoglobulin isotype (IgA, IgD, IgM, IgG) blood. repertoires duodenal papilla comprised same paired samples. after 4 8 weeks corticosteroid therapy contribution total marginalized, mirroring sharp declines titers regression clinical symptoms. Conclusion: finding highly abundant tissue active IAC, which disappear upon treatment, suggests specific responses are pivotal pathogenesis IAC.