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Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus
Osteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic l...
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Published in: | Arthritis research & therapy 2013-01, Vol.15 (1), p.R18-R18, Article R18 |
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creator | Rullo, Ornella J Woo, Jennifer M P Parsa, Miriam F Hoftman, Alice D C Maranian, Paul Elashoff, David A Niewold, Timothy B Grossman, Jennifer M Hahn, Bevra H McMahon, Maureen McCurdy, Deborah K Tsao, Betty P |
description | Osteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic lupus erythematosus (pSLE) and compared it to circulating plasma neutrophil gelatinase-associated lipocalin (cNGAL), a predictor of increased SLE disease activity.
cOPN and cNGAL were measured in prospectively followed pSLE (n=42) and adult SLE (aSLE; n=23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI).
Compared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P=0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r=0.51 and 0.52, P=0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P=0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P=0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%).
High circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts. |
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cOPN and cNGAL were measured in prospectively followed pSLE (n=42) and adult SLE (aSLE; n=23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI).
Compared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P=0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r=0.51 and 0.52, P=0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P=0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P=0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%).
High circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts.</description><identifier>ISSN: 1478-6354</identifier><identifier>EISSN: 1478-6362</identifier><identifier>EISSN: 1478-6354</identifier><identifier>DOI: 10.1186/ar4150</identifier><identifier>PMID: 23343383</identifier><language>eng</language><publisher>England: BioMed Central</publisher><subject>Acute-Phase Proteins ; Adolescent ; Adult ; Child ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Lipocalin-2 ; Lipocalins - blood ; Lupus Erythematosus, Systemic - blood ; Lupus Erythematosus, Systemic - pathology ; Male ; Osteopontin - blood ; Proto-Oncogene Proteins - blood ; Sensitivity and Specificity ; Severity of Illness Index</subject><ispartof>Arthritis research & therapy, 2013-01, Vol.15 (1), p.R18-R18, Article R18</ispartof><rights>Copyright © 2013 Rullo et al.; licensee BioMed Central Ltd. 2013 Rullo et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c366t-fcdd23341348b795b64d2ab6a4f487905e5809f77083cbd7a36537868265e8143</citedby><cites>FETCH-LOGICAL-c366t-fcdd23341348b795b64d2ab6a4f487905e5809f77083cbd7a36537868265e8143</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/PMC3672798/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672798/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23343383$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rullo, Ornella J</creatorcontrib><creatorcontrib>Woo, Jennifer M P</creatorcontrib><creatorcontrib>Parsa, Miriam F</creatorcontrib><creatorcontrib>Hoftman, Alice D C</creatorcontrib><creatorcontrib>Maranian, Paul</creatorcontrib><creatorcontrib>Elashoff, David A</creatorcontrib><creatorcontrib>Niewold, Timothy B</creatorcontrib><creatorcontrib>Grossman, Jennifer M</creatorcontrib><creatorcontrib>Hahn, Bevra H</creatorcontrib><creatorcontrib>McMahon, Maureen</creatorcontrib><creatorcontrib>McCurdy, Deborah K</creatorcontrib><creatorcontrib>Tsao, Betty P</creatorcontrib><title>Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus</title><title>Arthritis research & therapy</title><addtitle>Arthritis Res Ther</addtitle><description>Osteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic lupus erythematosus (pSLE) and compared it to circulating plasma neutrophil gelatinase-associated lipocalin (cNGAL), a predictor of increased SLE disease activity.
cOPN and cNGAL were measured in prospectively followed pSLE (n=42) and adult SLE (aSLE; n=23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI).
Compared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P=0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r=0.51 and 0.52, P=0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P=0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P=0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%).
High circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts.</description><subject>Acute-Phase Proteins</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Child</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Humans</subject><subject>Lipocalin-2</subject><subject>Lipocalins - blood</subject><subject>Lupus Erythematosus, Systemic - blood</subject><subject>Lupus Erythematosus, Systemic - pathology</subject><subject>Male</subject><subject>Osteopontin - blood</subject><subject>Proto-Oncogene Proteins - blood</subject><subject>Sensitivity and Specificity</subject><subject>Severity of Illness Index</subject><issn>1478-6354</issn><issn>1478-6362</issn><issn>1478-6354</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpVkc1L5EAQxZvFZdXZ9U-QPomXcfu7OxdBxC8Q3MN6bipJZ2xN0rErEea_N8PooKd6UL969eARcsTZGefO_IWsuGY_yAFX1i2NNGJvp7XaJ4eIz4wJUQj1i-wLKZWUTh6Q1b8WsAPahrfQIk0NTTiGNKR-jD2NdZhns6YDjHGWSGGkOeILbVKmKa-gpzV0sAp0pnE9n3axou00TEhDXo9PoYMx4YS_yc8GWgx_PuaCPF5f_b-8Xd4_3NxdXtwvK2nMuGyqut6E41K50ha6NKoWUBpQjXK2YDpox4rGWuZkVdYWpNHSOuOE0cFxJRfkfOs7TGUX6moOnaH1Q44d5LVPEP33TR-f_Cq9eWmssIWbDU4_DHJ6nQKOvotYhbaFPqQJPdeaM8GN0DN6skWrnBBzaHZvOPObVvy2lRk8_hpqh33WIN8BL3qJfg</recordid><startdate>20130123</startdate><enddate>20130123</enddate><creator>Rullo, Ornella J</creator><creator>Woo, Jennifer M P</creator><creator>Parsa, Miriam F</creator><creator>Hoftman, Alice D C</creator><creator>Maranian, Paul</creator><creator>Elashoff, David A</creator><creator>Niewold, Timothy B</creator><creator>Grossman, Jennifer M</creator><creator>Hahn, Bevra H</creator><creator>McMahon, Maureen</creator><creator>McCurdy, Deborah K</creator><creator>Tsao, Betty P</creator><general>BioMed Central</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130123</creationdate><title>Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus</title><author>Rullo, Ornella J ; Woo, Jennifer M P ; Parsa, Miriam F ; Hoftman, Alice D C ; Maranian, Paul ; Elashoff, David A ; Niewold, Timothy B ; Grossman, Jennifer M ; Hahn, Bevra H ; McMahon, Maureen ; McCurdy, Deborah K ; Tsao, Betty P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-fcdd23341348b795b64d2ab6a4f487905e5809f77083cbd7a36537868265e8143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute-Phase Proteins</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Child</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Humans</topic><topic>Lipocalin-2</topic><topic>Lipocalins - blood</topic><topic>Lupus Erythematosus, Systemic - blood</topic><topic>Lupus Erythematosus, Systemic - pathology</topic><topic>Male</topic><topic>Osteopontin - blood</topic><topic>Proto-Oncogene Proteins - blood</topic><topic>Sensitivity and Specificity</topic><topic>Severity of Illness Index</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rullo, Ornella J</creatorcontrib><creatorcontrib>Woo, Jennifer M P</creatorcontrib><creatorcontrib>Parsa, Miriam F</creatorcontrib><creatorcontrib>Hoftman, Alice D C</creatorcontrib><creatorcontrib>Maranian, Paul</creatorcontrib><creatorcontrib>Elashoff, David A</creatorcontrib><creatorcontrib>Niewold, Timothy B</creatorcontrib><creatorcontrib>Grossman, Jennifer M</creatorcontrib><creatorcontrib>Hahn, Bevra H</creatorcontrib><creatorcontrib>McMahon, Maureen</creatorcontrib><creatorcontrib>McCurdy, Deborah K</creatorcontrib><creatorcontrib>Tsao, Betty P</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Arthritis research & therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rullo, Ornella J</au><au>Woo, Jennifer M P</au><au>Parsa, Miriam F</au><au>Hoftman, Alice D C</au><au>Maranian, Paul</au><au>Elashoff, David A</au><au>Niewold, Timothy B</au><au>Grossman, Jennifer M</au><au>Hahn, Bevra H</au><au>McMahon, Maureen</au><au>McCurdy, Deborah K</au><au>Tsao, Betty P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus</atitle><jtitle>Arthritis research & therapy</jtitle><addtitle>Arthritis Res Ther</addtitle><date>2013-01-23</date><risdate>2013</risdate><volume>15</volume><issue>1</issue><spage>R18</spage><epage>R18</epage><pages>R18-R18</pages><artnum>R18</artnum><issn>1478-6354</issn><eissn>1478-6362</eissn><eissn>1478-6354</eissn><abstract>Osteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic lupus erythematosus (pSLE) and compared it to circulating plasma neutrophil gelatinase-associated lipocalin (cNGAL), a predictor of increased SLE disease activity.
cOPN and cNGAL were measured in prospectively followed pSLE (n=42) and adult SLE (aSLE; n=23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI).
Compared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P=0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r=0.51 and 0.52, P=0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P=0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P=0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%).
High circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts.</abstract><cop>England</cop><pub>BioMed Central</pub><pmid>23343383</pmid><doi>10.1186/ar4150</doi><oa>free_for_read</oa></addata></record> |
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subjects | Acute-Phase Proteins Adolescent Adult Child Enzyme-Linked Immunosorbent Assay Female Humans Lipocalin-2 Lipocalins - blood Lupus Erythematosus, Systemic - blood Lupus Erythematosus, Systemic - pathology Male Osteopontin - blood Proto-Oncogene Proteins - blood Sensitivity and Specificity Severity of Illness Index |
title | Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus |
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