The Cellular and Molecular Bases of Allergy, Inflammation and Tissue Fibrosis in Patients with IgG4-related Disease
Journal
International journal of molecular sciences
Journal Volume
21
Journal Issue
14
Pages
5082
Date Issued
2020-07-18
Author(s)
Liao, Hsien-Tzung
Chen, Ming-Han
Lu, Cheng-Shiun
Tsai, Hung-Cheng
Tsai, Chang-Youh
Abstract
IgG4-related disease (IgG4-RD) is a spectrum of complex fibroinflammatory disorder with protean manifestations mimicking malignant neoplasms, infectious or non-infectious inflammatory process. The histopathologic features of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis together with increased in situ infiltration of IgG4 bearing-plasma cells which account for more than 40% of all IgG-producing B cells. IgG4-RD can also be diagnosed based on an elevated serum IgG4 level of more than 110 mg/dL (normal < 86.5 mg/mL in adult) in conjunction with protean clinical manifestations in various organs such as pancreato-hepatobiliary inflammation with/without salivary/lacrimal gland enlargement. In the present review, we briefly discuss the role of genetic predisposition, environmental factors and candidate autoantibodies in the pathogenesis of IgG4-RD. Then, we discuss in detail the immunological paradox of IgG4 antibody, the mechanism of modified Th2 response for IgG4 rather than IgE antibody production and the controversial issues in the allergic reactions of IgG4-RD. Finally, we extensively review the implications of different immune-related cells, cytokines/chemokines/growth factors and Toll-like as well as NOD-like receptors in the pathogenesis of tissue fibro-inflammatory reactions. Our proposals for the future investigations and prospective therapeutic strategies for IgG4-RD are shown in the last part.
Subjects
CD4+cytotoxic T cell; Fab–arm exchange; IgG4-related disease; fibroinflammatory disorder; follicular helper T cell; lymphoplasmacytic infiltration; modified Th2 response; obliterative phlebitis; storiform fibrosis
SDGs
Other Subjects
autoantibody; carbonate dehydratase; CD19 antigen; CD4 antigen; CD8 antigen; chemokine; cytokine; interleukin 13; interleukin 17; interleukin 18; interleukin 1alpha; interleukin 1beta; interleukin 33; interleukin 4; interleukin 5; interleukin 6; interleukin 7; interleukin 9; monocyte chemotactic protein 1; platelet derived growth factor B; rheumatoid factor; tumor necrosis factor; vasculotropin; immunoglobulin E; immunoglobulin G; nucleotide binding oligomerization domain like receptor; toll like receptor; allergy; antibody production; Article; autoimmune disease; autoimmune pancreatitis; complement activation; DNA methylation; DNA sequencing; dysbiosis; environmental factor; eosinophilia; fibrosis; genetic predisposition; genetic regulation; genome-wide association study; glycosylation; hepatobiliary system inflammation; high throughput sequencing; histopathology; human; hypocomplementemia; immune response; immunoglobulin G4 related disease; immunoglobulin production; immunopathogenesis; inflammation; innate immunity; lymphocytic infiltration; membranous glomerulonephritis; molecular biology; myasthenia gravis; nonhuman; plasmablast; primary sclerosing cholangitis; regulatory T lymphocyte; Sjoegren syndrome; systemic lupus erythematosus; Th2 cell; animal; B lymphocyte; chemistry; fibrosis; genetics; hypersensitivity; immunology; inflammation; pathology; plasma cell; T lymphocyte; Animals; Autoimmune Diseases; B-Lymphocytes; Fibrosis; Humans; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Immunoglobulin G4-Related Disease; Inflammation; NLR Proteins; Plasma Cells; T-Lymphocytes; Toll-Like Receptors
Publisher
MDPI
Type
review