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Gastrointestinal and Extra-Intestinal Manifestations of IgG4-Related Disease. Miyabe Katsuyuki,Zen Yoh,Cornell Lynn D,Rajagopalan Govindarajan,Chowdhary Vaidehi R,Roberts Lewis R,Chari Suresh T Gastroenterology IgG4-related disease (IgG4-RD) is a chronic relapsing multi-organ fibro-inflammatory syndrome of presumed autoimmune etiology. It is characterized by increased serum levels of IgG4 and tissue infiltration by IgG4 cells. Increased titers of autoantibodies against a spectrum of self-antigens and response to steroids have led to its characterization as an autoimmune disease. However, the pathognomonic antigens probably differ among manifestations, and different antigens or autoantibodies produce similar immune reactions in different organs. Little is known about the pathogenic effects, if any, of serum IgG4 or IgG4 plasma cells in tissues. Despite several animal models of the disease, none truly recapitulates human IgG4-RD. Histologic analyses of tissues from patients with IgG4-RD reveal a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells, storiform fibrosis, and obliterative phlebitis, although these features vary among organs. Typical presentation and imaging findings include mass-forming synchronous or metachronous lesions in almost any organ, but most commonly in the pancreas, bile duct, retroperitoneum, kidneys, lungs, salivary and lacrimal glands, orbit, and lymph nodes. In all organs, inflammation can be reduced by corticosteroids and drugs that deplete B cells, such as rituximab. Patients with IgG4-RD have relapses that respond to primary therapy. Intense fibrosis accompanies the inflammatory response, leading to permanent organ damage and insufficiency. Death from IgG4-RD is rare. IgG4-RD is a multi-organ disease with predominant pancreatico-biliary involvement. Despite its relapsing-remitting course, patients have an excellent prognosis. 10.1053/j.gastro.2018.06.082
Genetic analysis of IgG4-related disease. Ishikawa Yuki,Terao Chikashi Modern rheumatology IgG4-related disease (IgG4-RD) is an emerging concept of a novel clinical entity, characterized by the swelling of the affected organs, increase in serum total IgG and IgG4 levels, infiltration of plasmacyte and eosinophil, fibrosis of the affected lesions and good response to corticosteroid. IgG4-RD includes diseases with organ-specific fibrosis and infiltration of IgG4-positive plasmacyte, previously known as type 1 autoimmune pancreatitis (AIP), Mikulicz's disease and others. Although the precise mechanisms of the pathogenesis of IgG4-RD are not yet understood, some studies have suggested genetic components contributing to the onset of IgG4-RD or its subgroup. The recent emergence of the concept of IgG4-RD has made it difficult to conduct genetic analyses of IgG4-RD as a whole. When the analyses are restricted to the various subgroups of IgG4-RD, they require a large number of DNA samples from patients satisfying IgG4-RD diagnostic criteria not completely overlapping the criteria in type 1 AIP, Mikulicz's disease and others. Not only HLA but also non-HLA genes have been described as IgG4-RD risk genes, particularly in type 1 AIP. In this mini-review article, we will explore previous studies analyzing genetic associations with IgG4-RD and its subgroups, and discuss the future direction of the research addressing the existing problems. 10.1080/14397595.2019.1621000