Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases

Koyabu, Masanori; Uchida, Kazushige; Miyoshi, Hideaki; Sakaguchi, Yutaku; Fukui, Toshiro; Ikeda, Hiroki; Takaoka, Makoto; Hirohara, Junko; Nishio, Akiyoshi; Uemura, Yoshiko; Üemoto, Shinji; Okazaki, Kazuichi

doi:10.1007/s00535-010-0199-3

Cited by 86 publications

(56 citation statements)

References 58 publications

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“…CD25? Tregs has been observed in bile duct tissue with ISC, along with the overexpression of two regulatory cytokines (IL-10 and TGF-b) [105,112]. IL-10 is suspected to participate in an IgG4 class-switch in B cells.…”

Section: T Cell Responsementioning

confidence: 99%

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IgG4-related sclerosing cholangitis: all we need to know

2016

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Our knowledge and experience of IgG4-related sclerosing cholangitis (ISC) have expanded in the last decade. ISC is one of the common organ manifestations of IgG4-related disease (IgG4-RD); approximately 60 % of patients with this systemic condition have ISC in the proximal and/or distal bile ducts. ISC needs to be discriminated from primary sclerosing cholangitis, cholangiocarcinoma, and other rare forms of lymphoplasmacytic cholangiopathy (e.g., follicular cholangitis and sclerosing cholangitis with granulocytic epithelial lesions). Its diagnosis requires a multidisciplinary approach, in which serology, histology, and imaging play crucial roles. Treatments with high-dose corticosteroids typically lead to the rapid and consistent induction of disease remission. Another promising therapeutic approach is B-cell depletion with rituximab. Although disease relapse is relatively common, provided that appropriate treatments are administered, ISC is considered a ''benign'' disease with a low risk of liver failure and biliary malignancy. Its molecular pathology is characterized by Th2-dominant immune reactions, regulatory T-cell activation, and CCL1-CCR8 interactions. Particular subsets of B cells such as plasmablasts and regulatory B cells also expand. A recent global proteomic study demonstrated that three significantly activated immunological cascades in ISC were all B-cell-or immunoglobulin-related (Fc-gamma receptormediated phagocytosis, B-cell receptor signaling pathway, and Fc-epsilon receptor I signaling pathway), suggesting the crucial roles of B cells in the underlying immune reactions. Despite the expansion of our knowledge of the pathophysiology of ISC, the exact role of IgG4 remains unclear. A better understanding of its immunopathology will offer some potential drug targets for this emerging biliary disease.

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Section: T Cell Responsementioning

confidence: 99%

“…CD38? plasmablasts in IgG4-RD [112,121]. Circulating plasmablasts are largely IgG4-positive, and have undergone extensive somatic hypermutation [121,122].…”

Section: Expansion Of B-cell Subsetsmentioning

confidence: 99%

IgG4-related sclerosing cholangitis: all we need to know

2016

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“…The ratio of IgG4 to IgG1-positive plasma cells was significantly higher in specimens obtained from patients with IgG4-SC than in those with PSC, autoimmune hepatitis, and PBC. 15 However, PSC and cholangiocarcinoma sometimes show infiltration of IgG4-positive plasma cells. 8,16 PSC with an infiltration of abundant IgG4-positive plasma cells in the liver was unresponsive to steroid therapy.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Steroid Administration for Diagnosis of IgG4-Related Sclerosing Cholangitis

Kubo

Suzuki

Kobayashi

et al. 2012

International Surgery

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Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is one of the IgG4-related systemic sclerosing diseases and responds well to steroid therapy. A 58-year-old male was admitted with hilar bile duct stenosis revealed by computed tomography. We performed percutaneous transhepatic right portal vein embolization (PTPE) and scheduled a right hepatectomy because a hilar cholangiocarcinoma was first suspected. However, there was no cytologic evidence of malignancy and serum IgG4 was elevated. Steroid therapy was initiated after PTPE. There was no evidence of bile duct stenosis after 4 weeks. Improving diagnostic technique, IgG4-SC was diagnosed and treated with steroid therapy. In some cases, we couldn't deny the malignancy and performed unnecessary resection. We recommend that steroid administration while waiting for the liver volume to increase after PTPE is useful. The therapy aids in the diagnosis of bile duct stenosis, which has value for a hilar bile duct limit type of IgG4-SC, as in the case reported here.

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“…18 Treg cells (as defined by immunohistochemical expression of the Treg-related transcription factor Foxp3) are also increased in liver biopsies from patients with IgG4-RD. 19 These findings suggest a possible model 10,20 in which an unknown immunologic trigger induces an aberrant Th2-type immune response leading to peripheral blood and tissue eosinophilia and increased IgE production. At the same time, Treg cells, perhaps to ameliorate the Th2 response, are stimulated to secrete IL-10, which (along with IL-4) induces class switching to IgG4, and TGF-b, a known stimulator of fibroblast activity.…”

Section: Pathophysiologymentioning

confidence: 91%

IgG4-Related Disease: A Reminder for Practicing Pathologists

Weindorf

Frederiksen

2017

Archives of Pathology &Amp; Laboratory Medicine

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IgG4-related disease (IgG4-RD) is a systemic autoimmune fibroinflammatory disease that produces sclerotic, tumefactive masses containing dense lymphoplasmacytic infiltrates rich in immunoglobulin (Ig) G4+ plasma cells. Initially characterized as a form of autoimmune pancreatitis, the distinctive histopathology of IgG4-RD has now been described in almost every organ system. However, because the clinical manifestations of IgG4-RD are diverse and nonspecific, the disease may go unsuspected until a biopsy or resection specimen is obtained to diagnose a presumed malignancy. Pathologists thus play a key role in the diagnosis of IgG4-RD, and familiarity with its histopathologic features is essential to preventing the irreversible comorbidities associated with this treatable disease. This brief review outlines the epidemiology, clinical manifestations, and histopathology of IgG4-RD, with the aim of furthering pathologists' awareness of and ability to diagnose this disorder.

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Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases

Cited by 86 publications

References 58 publications

IgG4-related sclerosing cholangitis: all we need to know

IgG4-related sclerosing cholangitis: all we need to know

Usefulness of Steroid Administration for Diagnosis of IgG4-Related Sclerosing Cholangitis

IgG4-Related Disease: A Reminder for Practicing Pathologists

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