Role of Aberrant Glycosylation of IgA1 Molecules in the Pathogenesis of IgA Nephropathy
Studies of the properties of immune complexes (IC) in the circulation, urine, and mesangium of IgA nephropathy (IgAN) patients have provided data relevant to the pathogenesis of this disease. IC contain predominantly polymeric IgA1 molecules which are deficient in galactose (Gal) residues on O-linke...
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| Veröffentlicht in: | Kidney & blood pressure research 2008-01, Vol.31 (1), p.29-37 |
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| creator | Mestecky, J. Tomana, M. Moldoveanu, Z. Julian, B.A. Suzuki, H. Matousovic, K. Renfrow, M.B. Novak, L. Wyatt, R.J. Novak, J. |
| description | Studies of the properties of immune complexes (IC) in the circulation, urine, and mesangium of IgA nephropathy (IgAN) patients have provided data relevant to the pathogenesis of this disease. IC contain predominantly polymeric IgA1 molecules which are deficient in galactose (Gal) residues on O-linked glycan chains in the hinge region (HR) of their heavy (H) chains. As a result of this aberrancy, a novel antigenic determinant(s) involving N-acetylgalactosamine (GalNAc) and perhaps sialic acid (SA) of O-linked glycans is generated and recognized by naturally occurring GalNAc-specific antibodies. Thus, IC in IgAN consist of Gal-deficient IgA1 molecules as an antigen, and GalNAc-specific IgG and/or IgA1 as an antibody. IgG antibodies to Gal-deficient IgA1 are probably induced by cross-reactive microbial antigens; they are present at variable levels not only in humans with or without IgAN but also in many phylogenetically diverse vertebrate species. Incubation of human mesangial cells with IC from sera of IgAN patients indicated that stimulation of cellular proliferative activity was restricted to the large (>800 kDa) complexes. These findings suggest that experimental approaches that prevent the formation of large Gal-deficient IgA1-IgG IC may be applied ultimately in an immunologically mediated therapy. |
| doi_str_mv | 10.1159/000112922 |
| format | Article |
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IC contain predominantly polymeric IgA1 molecules which are deficient in galactose (Gal) residues on O-linked glycan chains in the hinge region (HR) of their heavy (H) chains. As a result of this aberrancy, a novel antigenic determinant(s) involving N-acetylgalactosamine (GalNAc) and perhaps sialic acid (SA) of O-linked glycans is generated and recognized by naturally occurring GalNAc-specific antibodies. Thus, IC in IgAN consist of Gal-deficient IgA1 molecules as an antigen, and GalNAc-specific IgG and/or IgA1 as an antibody. IgG antibodies to Gal-deficient IgA1 are probably induced by cross-reactive microbial antigens; they are present at variable levels not only in humans with or without IgAN but also in many phylogenetically diverse vertebrate species. Incubation of human mesangial cells with IC from sera of IgAN patients indicated that stimulation of cellular proliferative activity was restricted to the large (>800 kDa) complexes. These findings suggest that experimental approaches that prevent the formation of large Gal-deficient IgA1-IgG IC may be applied ultimately in an immunologically mediated therapy.</description><identifier>ISSN: 1420-4096</identifier><identifier>EISSN: 1423-0143</identifier><identifier>DOI: 10.1159/000112922</identifier><identifier>PMID: 18182777</identifier><identifier>CODEN: RPBIEL</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Animals ; Glomerulonephritis, IGA - immunology ; Glomerulonephritis, IGA - metabolism ; Glomerulonephritis, IGA - pathology ; Glycosylation ; Humans ; Immunoglobulin A - metabolism ; Immunoglobulin A - physiology ; Review</subject><ispartof>Kidney & blood pressure research, 2008-01, Vol.31 (1), p.29-37</ispartof><rights>2008 S. Karger AG, Basel</rights><rights>(c) 2008 S. Karger AG, Basel</rights><rights>Copyright (c) 2008 S. Karger AG, Basel</rights><rights>Copyright © 2008 by S. Karger AG, Basel 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-9dd00865223eacae16120d6d59415d26acca711e85bebff08169e8eb1e50656c3</citedby><cites>FETCH-LOGICAL-c518t-9dd00865223eacae16120d6d59415d26acca711e85bebff08169e8eb1e50656c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,782,786,887,2433,27933,27934</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18182777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mestecky, J.</creatorcontrib><creatorcontrib>Tomana, M.</creatorcontrib><creatorcontrib>Moldoveanu, Z.</creatorcontrib><creatorcontrib>Julian, B.A.</creatorcontrib><creatorcontrib>Suzuki, H.</creatorcontrib><creatorcontrib>Matousovic, K.</creatorcontrib><creatorcontrib>Renfrow, M.B.</creatorcontrib><creatorcontrib>Novak, L.</creatorcontrib><creatorcontrib>Wyatt, R.J.</creatorcontrib><creatorcontrib>Novak, J.</creatorcontrib><title>Role of Aberrant Glycosylation of IgA1 Molecules in the Pathogenesis of IgA Nephropathy</title><title>Kidney & blood pressure research</title><addtitle>Kidney Blood Press Res</addtitle><description>Studies of the properties of immune complexes (IC) in the circulation, urine, and mesangium of IgA nephropathy (IgAN) patients have provided data relevant to the pathogenesis of this disease. IC contain predominantly polymeric IgA1 molecules which are deficient in galactose (Gal) residues on O-linked glycan chains in the hinge region (HR) of their heavy (H) chains. As a result of this aberrancy, a novel antigenic determinant(s) involving N-acetylgalactosamine (GalNAc) and perhaps sialic acid (SA) of O-linked glycans is generated and recognized by naturally occurring GalNAc-specific antibodies. Thus, IC in IgAN consist of Gal-deficient IgA1 molecules as an antigen, and GalNAc-specific IgG and/or IgA1 as an antibody. IgG antibodies to Gal-deficient IgA1 are probably induced by cross-reactive microbial antigens; they are present at variable levels not only in humans with or without IgAN but also in many phylogenetically diverse vertebrate species. Incubation of human mesangial cells with IC from sera of IgAN patients indicated that stimulation of cellular proliferative activity was restricted to the large (>800 kDa) complexes. These findings suggest that experimental approaches that prevent the formation of large Gal-deficient IgA1-IgG IC may be applied ultimately in an immunologically mediated therapy.</description><subject>Animals</subject><subject>Glomerulonephritis, IGA - immunology</subject><subject>Glomerulonephritis, IGA - metabolism</subject><subject>Glomerulonephritis, IGA - pathology</subject><subject>Glycosylation</subject><subject>Humans</subject><subject>Immunoglobulin A - metabolism</subject><subject>Immunoglobulin A - physiology</subject><subject>Review</subject><issn>1420-4096</issn><issn>1423-0143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqF0cFu1DAQBmALUdFSOHBHKOKAxCFlZhI7zgVpVUFbqQWEQBwtx5nspmTjxU6Q9u3xsqsWuHCypfn8yzMjxDOEM0RZvwEARKqJHogTLKnIAcvi4e875CXU6lg8jvE2MQlAj8QxatRUVdWJ-PbZD5z5Lls0HIIdp-xi2Doft4Odej_uKlfLBWY3ibl54Jj1YzatOPtkp5Vf8sixjweVfeDNKvhNqmyfiKPODpGfHs5T8fX9uy_nl_n1x4ur88V17iTqKa_bFkArSVSwdZZRIUGrWlmXKFtS1jlbIbKWDTddBxpVzZobZAlKKlecirf73M3crLl1PE7BDmYT-rUNW-Ntb_6ujP3KLP1PQ5rSkGQKeHUICP7HzHEy6z46HgY7sp-jqaAoylLRfyFBTYXSu8SX_8BbP4cxTcEQlYiJ7NJe75ELPsbA3d2XEcxuqeZuqcm--LPHe3nYYgLP9-C7DUsO92D__hfaIKSV</recordid><startdate>20080101</startdate><enddate>20080101</enddate><creator>Mestecky, J.</creator><creator>Tomana, M.</creator><creator>Moldoveanu, Z.</creator><creator>Julian, B.A.</creator><creator>Suzuki, H.</creator><creator>Matousovic, K.</creator><creator>Renfrow, M.B.</creator><creator>Novak, L.</creator><creator>Wyatt, R.J.</creator><creator>Novak, J.</creator><general>S. 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IC contain predominantly polymeric IgA1 molecules which are deficient in galactose (Gal) residues on O-linked glycan chains in the hinge region (HR) of their heavy (H) chains. As a result of this aberrancy, a novel antigenic determinant(s) involving N-acetylgalactosamine (GalNAc) and perhaps sialic acid (SA) of O-linked glycans is generated and recognized by naturally occurring GalNAc-specific antibodies. Thus, IC in IgAN consist of Gal-deficient IgA1 molecules as an antigen, and GalNAc-specific IgG and/or IgA1 as an antibody. IgG antibodies to Gal-deficient IgA1 are probably induced by cross-reactive microbial antigens; they are present at variable levels not only in humans with or without IgAN but also in many phylogenetically diverse vertebrate species. Incubation of human mesangial cells with IC from sera of IgAN patients indicated that stimulation of cellular proliferative activity was restricted to the large (>800 kDa) complexes. These findings suggest that experimental approaches that prevent the formation of large Gal-deficient IgA1-IgG IC may be applied ultimately in an immunologically mediated therapy.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>18182777</pmid><doi>10.1159/000112922</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Glomerulonephritis, IGA - immunology Glomerulonephritis, IGA - metabolism Glomerulonephritis, IGA - pathology Glycosylation Humans Immunoglobulin A - metabolism Immunoglobulin A - physiology Review |
| title | Role of Aberrant Glycosylation of IgA1 Molecules in the Pathogenesis of IgA Nephropathy |
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