Identification of anti-retinal antibodies in patients with age-related macular degeneration
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrial counties. Recent findings indicate that the autoimmunity is involved in the pathogenesis of the disease. However, there is no autoantibody biomarker applied in a clinical setting for diagnosis and pro...
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| Veröffentlicht in: | Experimental and molecular pathology 2012-10, Vol.93 (2), p.193-199 |
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| creator | Morohoshi, Kei Ohbayashi, Masaharu Patel, Nishal Chong, Victor Bird, Alan C. Ono, Santa J. |
| description | Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrial counties. Recent findings indicate that the autoimmunity is involved in the pathogenesis of the disease. However, there is no autoantibody biomarker applied in a clinical setting for diagnosis and prognosis of AMD.
In order to reveal retinal antigens targeted by serum IgG from AMD patients, mouse retinal tissue proteins were separated by 2-dimensional electrophoresis and the proteins in the immunoblots that were specific for dry and wet AMD patients IgG were identified by LC–MS/MS.
Retinol-binding protein 3 and aldolase C (ALDOC) were mainly recognized by IgG form wet AMD patients. Pyruvate kinase M2 (PKM2) was targeted by both dry and wet AMD and level of anti-PKM2 IgG antibody was correlated best with the stage of AMD. Expression of ALDOC and PKM2 was decreased in mouse retina from aging whereas PKM2 deposit on RPE was increased in aged mice.
Our data demonstrate that sera of AMD patients contain autoantibodies against retinal proteins and anti-PKM2 IgG serves as a biomarker for diagnosis and prognosis of AMD. Further investigation of the association of anti-retinal antibody level with expression level of antigens in retina will be needed to reveal the disease pathogenesis. |
| doi_str_mv | 10.1016/j.yexmp.2012.03.007 |
| format | Article |
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In order to reveal retinal antigens targeted by serum IgG from AMD patients, mouse retinal tissue proteins were separated by 2-dimensional electrophoresis and the proteins in the immunoblots that were specific for dry and wet AMD patients IgG were identified by LC–MS/MS.
Retinol-binding protein 3 and aldolase C (ALDOC) were mainly recognized by IgG form wet AMD patients. Pyruvate kinase M2 (PKM2) was targeted by both dry and wet AMD and level of anti-PKM2 IgG antibody was correlated best with the stage of AMD. Expression of ALDOC and PKM2 was decreased in mouse retina from aging whereas PKM2 deposit on RPE was increased in aged mice.
Our data demonstrate that sera of AMD patients contain autoantibodies against retinal proteins and anti-PKM2 IgG serves as a biomarker for diagnosis and prognosis of AMD. Further investigation of the association of anti-retinal antibody level with expression level of antigens in retina will be needed to reveal the disease pathogenesis.</description><identifier>ISSN: 0014-4800</identifier><identifier>EISSN: 1096-0945</identifier><identifier>DOI: 10.1016/j.yexmp.2012.03.007</identifier><identifier>PMID: 22465421</identifier><identifier>CODEN: EXMPA6</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Age-related macular degeneration ; Aged ; Aged, 80 and over ; Aldolase ; Animals ; Anti-retinal antibody ; Autoantibodies - blood ; Autoantibodies - isolation & purification ; Autoantibody profile ; Autoantigens - immunology ; Biological and medical sciences ; Biomarkers - blood ; Female ; Fructose-Bisphosphate Aldolase - immunology ; Geographic Atrophy - diagnosis ; Geographic Atrophy - immunology ; Humans ; Immunoglobulin G - immunology ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Mice ; Ophthalmology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Prognosis ; Pyruvate kinase ; Pyruvate Kinase - immunology ; Retina - immunology ; Retinol-Binding Proteins - immunology ; Retinopathies ; Wet Macular Degeneration - diagnosis ; Wet Macular Degeneration - immunology</subject><ispartof>Experimental and molecular pathology, 2012-10, Vol.93 (2), p.193-199</ispartof><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-60545cca9c45bfc7d774e7263e19e0cbd5efc44d94906c124d00919be018c3ab3</citedby><cites>FETCH-LOGICAL-c389t-60545cca9c45bfc7d774e7263e19e0cbd5efc44d94906c124d00919be018c3ab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.yexmp.2012.03.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26290697$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22465421$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morohoshi, Kei</creatorcontrib><creatorcontrib>Ohbayashi, Masaharu</creatorcontrib><creatorcontrib>Patel, Nishal</creatorcontrib><creatorcontrib>Chong, Victor</creatorcontrib><creatorcontrib>Bird, Alan C.</creatorcontrib><creatorcontrib>Ono, Santa J.</creatorcontrib><title>Identification of anti-retinal antibodies in patients with age-related macular degeneration</title><title>Experimental and molecular pathology</title><addtitle>Exp Mol Pathol</addtitle><description>Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrial counties. Recent findings indicate that the autoimmunity is involved in the pathogenesis of the disease. However, there is no autoantibody biomarker applied in a clinical setting for diagnosis and prognosis of AMD.
In order to reveal retinal antigens targeted by serum IgG from AMD patients, mouse retinal tissue proteins were separated by 2-dimensional electrophoresis and the proteins in the immunoblots that were specific for dry and wet AMD patients IgG were identified by LC–MS/MS.
Retinol-binding protein 3 and aldolase C (ALDOC) were mainly recognized by IgG form wet AMD patients. Pyruvate kinase M2 (PKM2) was targeted by both dry and wet AMD and level of anti-PKM2 IgG antibody was correlated best with the stage of AMD. Expression of ALDOC and PKM2 was decreased in mouse retina from aging whereas PKM2 deposit on RPE was increased in aged mice.
Our data demonstrate that sera of AMD patients contain autoantibodies against retinal proteins and anti-PKM2 IgG serves as a biomarker for diagnosis and prognosis of AMD. Further investigation of the association of anti-retinal antibody level with expression level of antigens in retina will be needed to reveal the disease pathogenesis.</description><subject>Age-related macular degeneration</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aldolase</subject><subject>Animals</subject><subject>Anti-retinal antibody</subject><subject>Autoantibodies - blood</subject><subject>Autoantibodies - isolation & purification</subject><subject>Autoantibody profile</subject><subject>Autoantigens - immunology</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Female</subject><subject>Fructose-Bisphosphate Aldolase - immunology</subject><subject>Geographic Atrophy - diagnosis</subject><subject>Geographic Atrophy - immunology</subject><subject>Humans</subject><subject>Immunoglobulin G - immunology</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Ophthalmology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Prognosis</subject><subject>Pyruvate kinase</subject><subject>Pyruvate Kinase - immunology</subject><subject>Retina - immunology</subject><subject>Retinol-Binding Proteins - immunology</subject><subject>Retinopathies</subject><subject>Wet Macular Degeneration - diagnosis</subject><subject>Wet Macular Degeneration - immunology</subject><issn>0014-4800</issn><issn>1096-0945</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v2zAMhoVhQ5Nm_QUFCl8G9GKPsmQ7OvQwBN0aIEAv7WkHQaboTIE_Uslpl39f5WPbbSeCwMOX5MPYNYeMAy-_brI9_e62WQ48z0BkANUHNuWgyhSULD6yKQCXqZwDTNhlCBsAUJG9YJM8l2Uhcz5lP5eW-tE1Ds3ohj4ZmsTEPvU0ut60x6YerKOQuD7ZRijiIXlz46_ErClyrRnJJp3BXWt8YmlNPflj2Gf2qTFtoKtznbHn7_dPi4d09fhjufi2SlHM1ZiWUMgC0SiURd1gZatKUpWXgrgiwNoW1KCUVkkFJfJc2vgHVzUBn6MwtZix21Pu1g8vOwqj7lxAalvT07ALmoMAUcTvy4iKE4p-CMFTo7fedcbvI6QPVvVGH63qg1UNQkercermvGBXd2T_zvzRGIEvZ8AENG3jTY8u_OPKPJ6uDkF3J46ijldHXgeMQpGs84SjtoP77yHvwKSXoA</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>Morohoshi, Kei</creator><creator>Ohbayashi, Masaharu</creator><creator>Patel, Nishal</creator><creator>Chong, Victor</creator><creator>Bird, Alan C.</creator><creator>Ono, Santa J.</creator><general>Elsevier Inc</general><general>Elsevier</general><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>20121001</creationdate><title>Identification of anti-retinal antibodies in patients with age-related macular degeneration</title><author>Morohoshi, Kei ; Ohbayashi, Masaharu ; Patel, Nishal ; Chong, Victor ; Bird, Alan C. ; Ono, Santa J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-60545cca9c45bfc7d774e7263e19e0cbd5efc44d94906c124d00919be018c3ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Age-related macular degeneration</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aldolase</topic><topic>Animals</topic><topic>Anti-retinal antibody</topic><topic>Autoantibodies - blood</topic><topic>Autoantibodies - isolation & purification</topic><topic>Autoantibody profile</topic><topic>Autoantigens - immunology</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Female</topic><topic>Fructose-Bisphosphate Aldolase - immunology</topic><topic>Geographic Atrophy - diagnosis</topic><topic>Geographic Atrophy - immunology</topic><topic>Humans</topic><topic>Immunoglobulin G - immunology</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Ophthalmology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Prognosis</topic><topic>Pyruvate kinase</topic><topic>Pyruvate Kinase - immunology</topic><topic>Retina - immunology</topic><topic>Retinol-Binding Proteins - immunology</topic><topic>Retinopathies</topic><topic>Wet Macular Degeneration - diagnosis</topic><topic>Wet Macular Degeneration - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morohoshi, Kei</creatorcontrib><creatorcontrib>Ohbayashi, Masaharu</creatorcontrib><creatorcontrib>Patel, Nishal</creatorcontrib><creatorcontrib>Chong, Victor</creatorcontrib><creatorcontrib>Bird, Alan C.</creatorcontrib><creatorcontrib>Ono, Santa J.</creatorcontrib><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>Experimental and molecular pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morohoshi, Kei</au><au>Ohbayashi, Masaharu</au><au>Patel, Nishal</au><au>Chong, Victor</au><au>Bird, Alan C.</au><au>Ono, Santa J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of anti-retinal antibodies in patients with age-related macular degeneration</atitle><jtitle>Experimental and molecular pathology</jtitle><addtitle>Exp Mol Pathol</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>93</volume><issue>2</issue><spage>193</spage><epage>199</epage><pages>193-199</pages><issn>0014-4800</issn><eissn>1096-0945</eissn><coden>EXMPA6</coden><abstract>Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrial counties. Recent findings indicate that the autoimmunity is involved in the pathogenesis of the disease. However, there is no autoantibody biomarker applied in a clinical setting for diagnosis and prognosis of AMD.
In order to reveal retinal antigens targeted by serum IgG from AMD patients, mouse retinal tissue proteins were separated by 2-dimensional electrophoresis and the proteins in the immunoblots that were specific for dry and wet AMD patients IgG were identified by LC–MS/MS.
Retinol-binding protein 3 and aldolase C (ALDOC) were mainly recognized by IgG form wet AMD patients. Pyruvate kinase M2 (PKM2) was targeted by both dry and wet AMD and level of anti-PKM2 IgG antibody was correlated best with the stage of AMD. Expression of ALDOC and PKM2 was decreased in mouse retina from aging whereas PKM2 deposit on RPE was increased in aged mice.
Our data demonstrate that sera of AMD patients contain autoantibodies against retinal proteins and anti-PKM2 IgG serves as a biomarker for diagnosis and prognosis of AMD. Further investigation of the association of anti-retinal antibody level with expression level of antigens in retina will be needed to reveal the disease pathogenesis.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>22465421</pmid><doi>10.1016/j.yexmp.2012.03.007</doi><tpages>7</tpages></addata></record> |
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| subjects | Age-related macular degeneration Aged Aged, 80 and over Aldolase Animals Anti-retinal antibody Autoantibodies - blood Autoantibodies - isolation & purification Autoantibody profile Autoantigens - immunology Biological and medical sciences Biomarkers - blood Female Fructose-Bisphosphate Aldolase - immunology Geographic Atrophy - diagnosis Geographic Atrophy - immunology Humans Immunoglobulin G - immunology Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Mice Ophthalmology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Prognosis Pyruvate kinase Pyruvate Kinase - immunology Retina - immunology Retinol-Binding Proteins - immunology Retinopathies Wet Macular Degeneration - diagnosis Wet Macular Degeneration - immunology |
| title | Identification of anti-retinal antibodies in patients with age-related macular degeneration |
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