Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality
Summary The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti‐CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti‐CL...
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| Veröffentlicht in: | Clinical and experimental immunology 2013-12, Vol.174 (3), p.441-448 |
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| creator | Frostegård, A. G. Hua, X. Su, J. Carrero, J. J. Heimbürger, O. Bárány, P. Stenvinkel, P. Frostegård, J. |
| description | Summary
The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti‐CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti‐CL and anti‐OxCL in HD‐patients. We conducted an observational study with a prospective follow‐up examining the relationship between anti‐CL, anti‐OxCL and mortality risk in a well‐characterized cohort of 221 prevalent HD patients [56% men, median age 66 (interquartile range 51–74) years, vintage time 29 (15–58) months] with a mean follow‐up period of 41 (20–48 months). According to the receiver operator characteristic (ROC) analysis, anti‐OxCL [area under the curve (AUC) 0·62, P |
| doi_str_mv | 10.1111/cei.12181 |
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The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti‐CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti‐CL and anti‐OxCL in HD‐patients. We conducted an observational study with a prospective follow‐up examining the relationship between anti‐CL, anti‐OxCL and mortality risk in a well‐characterized cohort of 221 prevalent HD patients [56% men, median age 66 (interquartile range 51–74) years, vintage time 29 (15–58) months] with a mean follow‐up period of 41 (20–48 months). According to the receiver operator characteristic (ROC) analysis, anti‐OxCL [area under the curve (AUC) 0·62, P < 0·01], but not anti‐CL (AUC 0·52, P = 0·2), is associated with mortality. In crude and adjusted Cox analysis, every log increase in anti‐OxCL inversely predicted all‐cause [adjusted hazard ratios (HR) 0·62 (0·43–0·89)] and CVD‐related [adjusted HR 0·56 (0·32–0·98)] mortality. Patients with anti‐OxCL levels below median also had increased all‐cause and cardiovascular disease (CVD)‐related mortality. Although anti‐OxCL and anti‐phosphorylcholine (PC) were related positively to each other (ρ = 0·57, P < 0·01), patients with one or two of these autoantibody levels below the median were associated with an incrementally increased death risk. Anti‐OxCL were co‐factor β2‐GPI‐independent; anti‐CL from patients with anti‐phospholipid antibody syndrome were β2‐GPI‐dependent, while sera from HD‐patients less so. Sera from healthy donors was not β2‐GPI‐dependent. Anti‐OxCL IgM is β2‐glycoprotein 1 (GPI)‐independent and a novel biomarker; low levels are associated with death among HD patients (and high levels with decreased risk). Combination with anti‐PC increases this association. Putative therapeutic implications warrant further investigation.</description><identifier>ISSN: 0009-9104</identifier><identifier>ISSN: 1365-2249</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1111/cei.12181</identifier><identifier>PMID: 23879320</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Age ; Aged ; antibodies ; Antibodies, Anticardiolipin - immunology ; Antiphospholipid Syndrome - blood ; Antiphospholipid Syndrome - immunology ; Apoptosis ; Atherosclerosis ; Autoantibodies - blood ; beta 2-Glycoprotein I ; Biomarkers ; cardiolipin ; Cardiolipins - immunology ; Cardiolipins - metabolism ; cardiovascular disease ; Cardiovascular Diseases - immunology ; Cardiovascular Diseases - mortality ; Cohort Studies ; Female ; haemodialysis ; Humans ; Immunoglobulin M - blood ; Immunoglobulin M - immunology ; inflammation ; Male ; Medical research ; Medicin och hälsovetenskap ; Middle Aged ; Mortality ; Original ; Prospective Studies ; Renal Dialysis - mortality ; Risk</subject><ispartof>Clinical and experimental immunology, 2013-12, Vol.174 (3), p.441-448</ispartof><rights>2013 British Society for Immunology</rights><rights>2013 British Society for Immunology.</rights><rights>Copyright © 2013 British Society for Immunology</rights><rights>Copyright © 2013 British Society for Immunology 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5641-fdb4b0fa80df15b5386e3e0afac3c371bd37160ed21d899c46efca56b6ae392c3</citedby><cites>FETCH-LOGICAL-c5641-fdb4b0fa80df15b5386e3e0afac3c371bd37160ed21d899c46efca56b6ae392c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826310/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826310/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,552,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23879320$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:127579434$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Frostegård, A. G.</creatorcontrib><creatorcontrib>Hua, X.</creatorcontrib><creatorcontrib>Su, J.</creatorcontrib><creatorcontrib>Carrero, J. J.</creatorcontrib><creatorcontrib>Heimbürger, O.</creatorcontrib><creatorcontrib>Bárány, P.</creatorcontrib><creatorcontrib>Stenvinkel, P.</creatorcontrib><creatorcontrib>Frostegård, J.</creatorcontrib><title>Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>Summary
The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti‐CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti‐CL and anti‐OxCL in HD‐patients. We conducted an observational study with a prospective follow‐up examining the relationship between anti‐CL, anti‐OxCL and mortality risk in a well‐characterized cohort of 221 prevalent HD patients [56% men, median age 66 (interquartile range 51–74) years, vintage time 29 (15–58) months] with a mean follow‐up period of 41 (20–48 months). According to the receiver operator characteristic (ROC) analysis, anti‐OxCL [area under the curve (AUC) 0·62, P < 0·01], but not anti‐CL (AUC 0·52, P = 0·2), is associated with mortality. In crude and adjusted Cox analysis, every log increase in anti‐OxCL inversely predicted all‐cause [adjusted hazard ratios (HR) 0·62 (0·43–0·89)] and CVD‐related [adjusted HR 0·56 (0·32–0·98)] mortality. Patients with anti‐OxCL levels below median also had increased all‐cause and cardiovascular disease (CVD)‐related mortality. Although anti‐OxCL and anti‐phosphorylcholine (PC) were related positively to each other (ρ = 0·57, P < 0·01), patients with one or two of these autoantibody levels below the median were associated with an incrementally increased death risk. Anti‐OxCL were co‐factor β2‐GPI‐independent; anti‐CL from patients with anti‐phospholipid antibody syndrome were β2‐GPI‐dependent, while sera from HD‐patients less so. Sera from healthy donors was not β2‐GPI‐dependent. Anti‐OxCL IgM is β2‐glycoprotein 1 (GPI)‐independent and a novel biomarker; low levels are associated with death among HD patients (and high levels with decreased risk). Combination with anti‐PC increases this association. Putative therapeutic implications warrant further investigation.</description><subject>Age</subject><subject>Aged</subject><subject>antibodies</subject><subject>Antibodies, Anticardiolipin - immunology</subject><subject>Antiphospholipid Syndrome - blood</subject><subject>Antiphospholipid Syndrome - immunology</subject><subject>Apoptosis</subject><subject>Atherosclerosis</subject><subject>Autoantibodies - blood</subject><subject>beta 2-Glycoprotein I</subject><subject>Biomarkers</subject><subject>cardiolipin</subject><subject>Cardiolipins - immunology</subject><subject>Cardiolipins - metabolism</subject><subject>cardiovascular disease</subject><subject>Cardiovascular Diseases - immunology</subject><subject>Cardiovascular Diseases - mortality</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>haemodialysis</subject><subject>Humans</subject><subject>Immunoglobulin M - blood</subject><subject>Immunoglobulin M - immunology</subject><subject>inflammation</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicin och hälsovetenskap</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Original</subject><subject>Prospective Studies</subject><subject>Renal Dialysis - mortality</subject><subject>Risk</subject><issn>0009-9104</issn><issn>1365-2249</issn><issn>1365-2249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqNkl1v0zAUhiMEYmVwwR9AlrjZJLL5K058MwlVAyoNcQPXluOcpN6cuNhJS_lN_Ei8tRsUaRKW_Hme97WPdbLsNcFnJLVzA_aMUFKRJ9mMMFHklHL5NJthjGUuCeZH2YsYr9NWCEGfZ0eUVaVkFM-yX4u-nwbfOV9Pzg7oZNGdfkZ6GG3tGwsR6U7bIY7I_7CN_QkNMjo01ju7SnQ9jWjwqevRruEgpAOk0Bocqq3vdbiBEFE6X2rok7N222gjWiUhDGN8h3SM3lg9phsG6O783BZt7LhEvQ-jdnbcvsyetdpFeLWfj7NvHy6_zj_lV18-Lubvr3JTCE7ytql5jVtd4aYlRV2wSgADrFttmGElqZs0CAwNJU0lpeECWqMLUQsNTFLDjrN85xs3sJpqtQo2ZbBVXlu1P7pJK1AFrTCTiZeP8qvgmz-ieyGhZVFKznjSXuy0CeihMek3gnaHFgeRwS5V59eKVVQwgpPByd4g-O8TxFH1NhpwTg_gp6gIF7wgrMLiP1BeElxhWSb07T_otZ_CkH5dkYLKgvOquL37dEeZ4GMM0D68m2B1W5oqlaa6K83Evvk70QfyvhYTcL4DNtbB9nEnNb9c7Cx_A2Ae9Jw</recordid><startdate>201312</startdate><enddate>201312</enddate><creator>Frostegård, A. G.</creator><creator>Hua, X.</creator><creator>Su, J.</creator><creator>Carrero, J. J.</creator><creator>Heimbürger, O.</creator><creator>Bárány, P.</creator><creator>Stenvinkel, P.</creator><creator>Frostegård, J.</creator><general>Oxford University Press</general><general>Blackwell Science Inc</general><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>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>201312</creationdate><title>Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality</title><author>Frostegård, A. G. ; Hua, X. ; Su, J. ; Carrero, J. J. ; Heimbürger, O. ; Bárány, P. ; Stenvinkel, P. ; Frostegård, J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5641-fdb4b0fa80df15b5386e3e0afac3c371bd37160ed21d899c46efca56b6ae392c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Age</topic><topic>Aged</topic><topic>antibodies</topic><topic>Antibodies, Anticardiolipin - immunology</topic><topic>Antiphospholipid Syndrome - blood</topic><topic>Antiphospholipid Syndrome - immunology</topic><topic>Apoptosis</topic><topic>Atherosclerosis</topic><topic>Autoantibodies - blood</topic><topic>beta 2-Glycoprotein I</topic><topic>Biomarkers</topic><topic>cardiolipin</topic><topic>Cardiolipins - immunology</topic><topic>Cardiolipins - metabolism</topic><topic>cardiovascular disease</topic><topic>Cardiovascular Diseases - immunology</topic><topic>Cardiovascular Diseases - mortality</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>haemodialysis</topic><topic>Humans</topic><topic>Immunoglobulin M - blood</topic><topic>Immunoglobulin M - immunology</topic><topic>inflammation</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicin och hälsovetenskap</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Original</topic><topic>Prospective Studies</topic><topic>Renal Dialysis - mortality</topic><topic>Risk</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Frostegård, A. G.</creatorcontrib><creatorcontrib>Hua, X.</creatorcontrib><creatorcontrib>Su, J.</creatorcontrib><creatorcontrib>Carrero, J. J.</creatorcontrib><creatorcontrib>Heimbürger, O.</creatorcontrib><creatorcontrib>Bárány, P.</creatorcontrib><creatorcontrib>Stenvinkel, P.</creatorcontrib><creatorcontrib>Frostegård, J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Clinical and experimental immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Frostegård, A. G.</au><au>Hua, X.</au><au>Su, J.</au><au>Carrero, J. J.</au><au>Heimbürger, O.</au><au>Bárány, P.</au><au>Stenvinkel, P.</au><au>Frostegård, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>2013-12</date><risdate>2013</risdate><volume>174</volume><issue>3</issue><spage>441</spage><epage>448</epage><pages>441-448</pages><issn>0009-9104</issn><issn>1365-2249</issn><eissn>1365-2249</eissn><abstract>Summary
The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti‐CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti‐CL and anti‐OxCL in HD‐patients. We conducted an observational study with a prospective follow‐up examining the relationship between anti‐CL, anti‐OxCL and mortality risk in a well‐characterized cohort of 221 prevalent HD patients [56% men, median age 66 (interquartile range 51–74) years, vintage time 29 (15–58) months] with a mean follow‐up period of 41 (20–48 months). According to the receiver operator characteristic (ROC) analysis, anti‐OxCL [area under the curve (AUC) 0·62, P < 0·01], but not anti‐CL (AUC 0·52, P = 0·2), is associated with mortality. In crude and adjusted Cox analysis, every log increase in anti‐OxCL inversely predicted all‐cause [adjusted hazard ratios (HR) 0·62 (0·43–0·89)] and CVD‐related [adjusted HR 0·56 (0·32–0·98)] mortality. Patients with anti‐OxCL levels below median also had increased all‐cause and cardiovascular disease (CVD)‐related mortality. Although anti‐OxCL and anti‐phosphorylcholine (PC) were related positively to each other (ρ = 0·57, P < 0·01), patients with one or two of these autoantibody levels below the median were associated with an incrementally increased death risk. Anti‐OxCL were co‐factor β2‐GPI‐independent; anti‐CL from patients with anti‐phospholipid antibody syndrome were β2‐GPI‐dependent, while sera from HD‐patients less so. Sera from healthy donors was not β2‐GPI‐dependent. Anti‐OxCL IgM is β2‐glycoprotein 1 (GPI)‐independent and a novel biomarker; low levels are associated with death among HD patients (and high levels with decreased risk). Combination with anti‐PC increases this association. Putative therapeutic implications warrant further investigation.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>23879320</pmid><doi>10.1111/cei.12181</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Age Aged antibodies Antibodies, Anticardiolipin - immunology Antiphospholipid Syndrome - blood Antiphospholipid Syndrome - immunology Apoptosis Atherosclerosis Autoantibodies - blood beta 2-Glycoprotein I Biomarkers cardiolipin Cardiolipins - immunology Cardiolipins - metabolism cardiovascular disease Cardiovascular Diseases - immunology Cardiovascular Diseases - mortality Cohort Studies Female haemodialysis Humans Immunoglobulin M - blood Immunoglobulin M - immunology inflammation Male Medical research Medicin och hälsovetenskap Middle Aged Mortality Original Prospective Studies Renal Dialysis - mortality Risk |
| title | Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality |
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