Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation
Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation. A minority of patients with Alport syndrome develop anti-GBM disease in their allografts after renal transplantation. Clinically, the renal disease appears indistinguishable from Goodpasture’s...
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Veröffentlicht in: | Kidney international 1998-03, Vol.53 (3), p.762-766 |
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description | Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation. A minority of patients with Alport syndrome develop anti-GBM disease in their allografts after renal transplantation. Clinically, the renal disease appears indistinguishable from Goodpasture’s disease of native kidneys, in which the target of autoantibodies has been identified as the NC1 domain of the α3 chain of type IV collagen, α3(IV)NC1. However, in the majority of cases, Alport syndrome is due to mutations in the gene encoding the α5 chain of type IV collagen, located on the X chromosome. Neither chain is detectable in the glomerular basement membrane (GBM) of most patients with Alport syndrome. We investigated the targets of the alloantibodies of 12 Alport patients who developed post-transplant anti-GBM disease by Western blotting onto recombinant NC1 domains made in insect cells. Binding to these antigens, for both typical Goodpasture and Alport anti-GBM antibodies, was strong and conformation-sensitive. Nine antibodies showed selective binding to α5(IV)NC1. This specificity was confirmed by the demonstration of binding to a 26kDa band of collagenase-solubilized human GBM, and/or binding to normal epidermal as well as renal basement membranes by indirect immunofluorescence. One antibody showed binding to α5 and α3(IV)NC1, while two showed predominant binding to α3(IV)NC1. All seven patients whose pedigree or mutation analysis showed X-linked inheritance had predominant anti-α5 reactivity. One with predominant anti-α3 reactivity had a COL4A3 mutation. These findings show that human anti-GBM disease can be associated with antibodies directed towards different molecular targets. α5(IV)NC1 is the primary target in most patients with X-linked Alport syndrome who develop post-transplant anti-GBM disease. |
doi_str_mv | 10.1046/j.1523-1755.1998.00794.x |
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Neil</creator><creatorcontrib>Brainwood, David ; Kashtan, Clifford ; Gubler, Marie Claire ; Turner, A. Neil</creatorcontrib><description>Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation. A minority of patients with Alport syndrome develop anti-GBM disease in their allografts after renal transplantation. Clinically, the renal disease appears indistinguishable from Goodpasture’s disease of native kidneys, in which the target of autoantibodies has been identified as the NC1 domain of the α3 chain of type IV collagen, α3(IV)NC1. However, in the majority of cases, Alport syndrome is due to mutations in the gene encoding the α5 chain of type IV collagen, located on the X chromosome. Neither chain is detectable in the glomerular basement membrane (GBM) of most patients with Alport syndrome. We investigated the targets of the alloantibodies of 12 Alport patients who developed post-transplant anti-GBM disease by Western blotting onto recombinant NC1 domains made in insect cells. Binding to these antigens, for both typical Goodpasture and Alport anti-GBM antibodies, was strong and conformation-sensitive. Nine antibodies showed selective binding to α5(IV)NC1. This specificity was confirmed by the demonstration of binding to a 26kDa band of collagenase-solubilized human GBM, and/or binding to normal epidermal as well as renal basement membranes by indirect immunofluorescence. One antibody showed binding to α5 and α3(IV)NC1, while two showed predominant binding to α3(IV)NC1. All seven patients whose pedigree or mutation analysis showed X-linked inheritance had predominant anti-α5 reactivity. One with predominant anti-α3 reactivity had a COL4A3 mutation. These findings show that human anti-GBM disease can be associated with antibodies directed towards different molecular targets. α5(IV)NC1 is the primary target in most patients with X-linked Alport syndrome who develop post-transplant anti-GBM disease.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1046/j.1523-1755.1998.00794.x</identifier><identifier>PMID: 9507224</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Alport syndrome ; Amino Acid Sequence ; anti-GBM disease ; Anti-Glomerular Basement Membrane Disease - etiology ; Anti-Glomerular Basement Membrane Disease - genetics ; Anti-Glomerular Basement Membrane Disease - immunology ; Base Sequence ; Basement Membrane - immunology ; Biological and medical sciences ; Collagen - genetics ; Collagen - immunology ; DNA Primers - genetics ; Goodpasture syndrome ; Humans ; immune system ; Isoantibodies - blood ; Isoantigens - genetics ; Kidney Glomerulus - immunology ; Kidney Transplantation - adverse effects ; Kidney Transplantation - immunology ; Medical sciences ; Nephritis, Hereditary - immunology ; Nephritis, Hereditary - surgery ; Surgery (general aspects). 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Neil</creatorcontrib><title>Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation. A minority of patients with Alport syndrome develop anti-GBM disease in their allografts after renal transplantation. Clinically, the renal disease appears indistinguishable from Goodpasture’s disease of native kidneys, in which the target of autoantibodies has been identified as the NC1 domain of the α3 chain of type IV collagen, α3(IV)NC1. However, in the majority of cases, Alport syndrome is due to mutations in the gene encoding the α5 chain of type IV collagen, located on the X chromosome. Neither chain is detectable in the glomerular basement membrane (GBM) of most patients with Alport syndrome. We investigated the targets of the alloantibodies of 12 Alport patients who developed post-transplant anti-GBM disease by Western blotting onto recombinant NC1 domains made in insect cells. Binding to these antigens, for both typical Goodpasture and Alport anti-GBM antibodies, was strong and conformation-sensitive. Nine antibodies showed selective binding to α5(IV)NC1. This specificity was confirmed by the demonstration of binding to a 26kDa band of collagenase-solubilized human GBM, and/or binding to normal epidermal as well as renal basement membranes by indirect immunofluorescence. One antibody showed binding to α5 and α3(IV)NC1, while two showed predominant binding to α3(IV)NC1. All seven patients whose pedigree or mutation analysis showed X-linked inheritance had predominant anti-α5 reactivity. One with predominant anti-α3 reactivity had a COL4A3 mutation. These findings show that human anti-GBM disease can be associated with antibodies directed towards different molecular targets. α5(IV)NC1 is the primary target in most patients with X-linked Alport syndrome who develop post-transplant anti-GBM disease.</description><subject>Alport syndrome</subject><subject>Amino Acid Sequence</subject><subject>anti-GBM disease</subject><subject>Anti-Glomerular Basement Membrane Disease - etiology</subject><subject>Anti-Glomerular Basement Membrane Disease - genetics</subject><subject>Anti-Glomerular Basement Membrane Disease - immunology</subject><subject>Base Sequence</subject><subject>Basement Membrane - immunology</subject><subject>Biological and medical sciences</subject><subject>Collagen - genetics</subject><subject>Collagen - immunology</subject><subject>DNA Primers - genetics</subject><subject>Goodpasture syndrome</subject><subject>Humans</subject><subject>immune system</subject><subject>Isoantibodies - blood</subject><subject>Isoantigens - genetics</subject><subject>Kidney Glomerulus - immunology</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Kidney Transplantation - immunology</subject><subject>Medical sciences</subject><subject>Nephritis, Hereditary - immunology</subject><subject>Nephritis, Hereditary - surgery</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the urinary system</subject><subject>transplantation</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE9v1DAQxS0EKtvCR0DyAXFLGMfxxj6Wij-VKnEpZ8txxpVXTrzYDirfHoddLUdO1sx7bzzzI4QyaBn0-4-HlomON2wQomVKyRZgUH37_ILsLsJLsgOQoukEl6_Jdc4HqLXicEWulICh6_od8Y8mPWHJNDpqQohmKX6Mk8dM_UJvwzGmQrdm8xTijGkNJtHRZJxxKXTGeUxmQTr5jLVJjSuYaMLFBFqqko-hhk3xcXlDXjkTMr49vzfkx5fPj3ffmofvX-_vbh8aK_aiNAqZE6NUFqXsmexHCbU209RZprjggxw7i0Ko3tTDJzB7uR955ySgcwiC35APp7nHFH-umIuefbYY6iIY16wHNXCugFWjPBltijkndPqY_GzSb81Ab5T1QW8w9QZTb5T1X8r6uUbfnf9YxxmnS_CMtervz7rJ1gRXSVifL7aOVRfAvzGLKWvCi973CkBtp3w66Vh5_fKYdLYeF4uTT2iLnqL__65_AKe7pwU</recordid><startdate>19980301</startdate><enddate>19980301</enddate><creator>Brainwood, David</creator><creator>Kashtan, Clifford</creator><creator>Gubler, Marie Claire</creator><creator>Turner, A. Neil</creator><general>Elsevier Inc</general><general>Nature Publishing</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19980301</creationdate><title>Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation</title><author>Brainwood, David ; Kashtan, Clifford ; Gubler, Marie Claire ; Turner, A. Neil</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c565t-9e1f5b89ce884184b80f5badd2c1935378b2ce5594a199d0a686b32f80effe053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Alport syndrome</topic><topic>Amino Acid Sequence</topic><topic>anti-GBM disease</topic><topic>Anti-Glomerular Basement Membrane Disease - etiology</topic><topic>Anti-Glomerular Basement Membrane Disease - genetics</topic><topic>Anti-Glomerular Basement Membrane Disease - immunology</topic><topic>Base Sequence</topic><topic>Basement Membrane - immunology</topic><topic>Biological and medical sciences</topic><topic>Collagen - genetics</topic><topic>Collagen - immunology</topic><topic>DNA Primers - genetics</topic><topic>Goodpasture syndrome</topic><topic>Humans</topic><topic>immune system</topic><topic>Isoantibodies - blood</topic><topic>Isoantigens - genetics</topic><topic>Kidney Glomerulus - immunology</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Kidney Transplantation - immunology</topic><topic>Medical sciences</topic><topic>Nephritis, Hereditary - immunology</topic><topic>Nephritis, Hereditary - surgery</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the urinary system</topic><topic>transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brainwood, David</creatorcontrib><creatorcontrib>Kashtan, Clifford</creatorcontrib><creatorcontrib>Gubler, Marie Claire</creatorcontrib><creatorcontrib>Turner, A. Neil</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brainwood, David</au><au>Kashtan, Clifford</au><au>Gubler, Marie Claire</au><au>Turner, A. Neil</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>1998-03-01</date><risdate>1998</risdate><volume>53</volume><issue>3</issue><spage>762</spage><epage>766</epage><pages>762-766</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation. A minority of patients with Alport syndrome develop anti-GBM disease in their allografts after renal transplantation. Clinically, the renal disease appears indistinguishable from Goodpasture’s disease of native kidneys, in which the target of autoantibodies has been identified as the NC1 domain of the α3 chain of type IV collagen, α3(IV)NC1. However, in the majority of cases, Alport syndrome is due to mutations in the gene encoding the α5 chain of type IV collagen, located on the X chromosome. Neither chain is detectable in the glomerular basement membrane (GBM) of most patients with Alport syndrome. We investigated the targets of the alloantibodies of 12 Alport patients who developed post-transplant anti-GBM disease by Western blotting onto recombinant NC1 domains made in insect cells. Binding to these antigens, for both typical Goodpasture and Alport anti-GBM antibodies, was strong and conformation-sensitive. Nine antibodies showed selective binding to α5(IV)NC1. This specificity was confirmed by the demonstration of binding to a 26kDa band of collagenase-solubilized human GBM, and/or binding to normal epidermal as well as renal basement membranes by indirect immunofluorescence. One antibody showed binding to α5 and α3(IV)NC1, while two showed predominant binding to α3(IV)NC1. All seven patients whose pedigree or mutation analysis showed X-linked inheritance had predominant anti-α5 reactivity. One with predominant anti-α3 reactivity had a COL4A3 mutation. These findings show that human anti-GBM disease can be associated with antibodies directed towards different molecular targets. α5(IV)NC1 is the primary target in most patients with X-linked Alport syndrome who develop post-transplant anti-GBM disease.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>9507224</pmid><doi>10.1046/j.1523-1755.1998.00794.x</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Alport syndrome Amino Acid Sequence anti-GBM disease Anti-Glomerular Basement Membrane Disease - etiology Anti-Glomerular Basement Membrane Disease - genetics Anti-Glomerular Basement Membrane Disease - immunology Base Sequence Basement Membrane - immunology Biological and medical sciences Collagen - genetics Collagen - immunology DNA Primers - genetics Goodpasture syndrome Humans immune system Isoantibodies - blood Isoantigens - genetics Kidney Glomerulus - immunology Kidney Transplantation - adverse effects Kidney Transplantation - immunology Medical sciences Nephritis, Hereditary - immunology Nephritis, Hereditary - surgery Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system transplantation |
title | Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation |
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