Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease
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...
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2014-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2014/197548 |
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| author | Colin Reily Hiroyuki Ueda Zhi-Qiang Huang Jiri Mestecky Bruce A. Julian Christopher D. Willey Jan Novak |
| author_facet | Colin Reily Hiroyuki Ueda Zhi-Qiang Huang Jiri Mestecky Bruce A. Julian Christopher D. Willey Jan Novak |
| author_sort | Colin Reily |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-018477dfc6d8451d87d2bf7e11f83da2 |
| institution | DOAJ |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-018477dfc6d8451d87d2bf7e11f83da22025-08-20T03:22:28ZengWileyJournal of Immunology Research2314-88612314-71562014-01-01201410.1155/2014/197548197548Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune DiseaseColin Reily0Hiroyuki Ueda1Zhi-Qiang Huang2Jiri Mestecky3Bruce A. Julian4Christopher D. Willey5Jan Novak6Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USADepartment of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USADepartment of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USADepartment of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USADepartment of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USADepartment of Radiation Oncology, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USADepartment of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 762, Birmingham, AL 35294, USAImmunoglobulin 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.http://dx.doi.org/10.1155/2014/197548 |
| spellingShingle | Colin Reily Hiroyuki Ueda Zhi-Qiang Huang Jiri Mestecky Bruce A. Julian Christopher D. Willey Jan Novak Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease Journal of Immunology Research |
| title | Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease |
| title_full | Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease |
| title_fullStr | Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease |
| title_full_unstemmed | Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease |
| title_short | Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease |
| title_sort | cellular signaling and production of galactose deficient iga1 in iga nephropathy an autoimmune disease |
| url | http://dx.doi.org/10.1155/2014/197548 |
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