title: Cellular signaling and production of galactose-deficient IgA1 in IgA nephropathy, an autoimmune disease.
abstract: Immunoglobulin A (IgA) nephropathy (IgAN), the leading cause of primary glomerulonephritis, is characterized by IgA1-containing immunodeposits in the glomeruli. IgAN is a chronic disease, with up to 40% of patients progressing to end-stage renal disease, with no disease-specific treatment. Multiple studies of the origin of the glomerular immunodeposits have linked elevated circulating levels of aberrantly glycosylated IgA1 (galactose-deficient in some O-glycans; Gd-IgA1) with formation of nephritogenic Gd-IgA1-containing immune complexes. Gd-IgA1 is recognized as an autoantigen in susceptible individuals by anti-glycan autoantibodies, resulting in immune complexes that may ultimately deposit in the kidney and induce glomerular injury. Genetic studies have revealed that an elevated level of Gd-IgA1 in the circulation of IgAN patients is a hereditable trait. Moreover, recent genome-wide association studies have identified several immunity-related loci that associated with IgAN. Production of Gd-IgA1 by IgA1-secreting cells of IgAN patients has been attributed to abnormal expression and activity of several key glycosyltransferases. Substantial evidence is emerging that abnormal signaling in IgA1-producing cells is related to the production of Gd-IgA1. As Gd-IgA1 is the key autoantigen in IgAN, understanding the genetic, biochemical, and environmental aspects of the abnormal signaling in IgA1-producing cells will provide insight into possible targets for future disease-specific therapy.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USA.
authors.forename: Colin
authors.identifier: 0000-0002-4033-1360
authors.initials: C
authors.lastname: Reily
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USA.
authors.forename: Hiroyuki
authors.identifier: 0000-0002-8282-7313
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USA.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Huang
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USA ; Department of Medicine, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA.
authors.forename: Jiri
authors.initials: J
authors.lastname: Mestecky
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USA ; Department of Medicine, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Julian
authors.affiliation: Department of Radiation Oncology, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA.
authors.forename: Christopher D
authors.identifier: 0000-0001-9953-0279
authors.initials: CD
authors.lastname: Willey
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USA.
authors.forename: Jan
authors.identifier: 0000-0002-9211-6670
authors.initials: J
authors.lastname: Novak
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007070:Immunoglobulin A; D016695:Glycosyltransferases; D005690:Galactose