Systemic disorders with rheumatic manifestations: Edited by John Stone and Arezou KhosroshahiPathogenesis of IgG4-related diseaseZen, Yoha; Nakanuma, Yasunib Author Information aInstitute of Liver Studies, King's College Hospital, London, UK bDepartment of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan Correspondence to Yoh Zen, MD, PhD, FRCPath, Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK Tel: +44 20 3299 3734; fax: +44 20 3299 3125; e-mail: [email protected] Current Opinion in Rheumatology: January 2011 - Volume 23 - Issue 1 - p 114-118 doi: 10.1097/BOR.0b013e3283412f4a Buy Metrics Abstract Purpose of review To review studies that have examined underlying genetic and immunological aspects of IgG4-related disease. Recent findings Genetic studies have suggested that several human leukocyte antigen (HLA) and non-HLA haplotypes/genotypes are associated with susceptibility to IgG4-related disease or to disease relapse after steroid therapy. Among several autoantibodies identified so far, autoantibodies against lactoferrin and carbonic anhydrase II are most frequently detected in serum of IgG4-disease patients. However, it has not been well clarified whether or not those autoantibodies belong to an IgG4 subclass. Studies that have demonstrated molecular mimicry between Helicobacter pylori and constituents of pancreatic epithelial cells suggest that gastric H. pylori infection triggers autoimmune pancreatitis in genetically predisposed individuals through antibody cross-reactivity. Recently, T-helper 2 immune reaction has been suggested to be predominant in IgG4-related disease. Interestingly, regulatory immune reactions are activated in IgG4-related disease, and regulatory cytokines interleukin-10 and transforming growth factor-β have been suggested, respectively, to play important roles in IgG4 class switch and fibroplasia. Summary Autoimmunity has been considered the most probable pathogenesis of IgG4-related disease, but has not been completely proved so far. A breakthrough study to detect a specific autoantigen, autoantibody, or pathogen is necessary. © 2011 Lippincott Williams & Wilkins, Inc.