Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease
There is currently no blood-based test for detection of early-stage osteoarthritis (OA) and the anti-cyclic citrullinated peptide (CCP) antibody test for rheumatoid arthritis (RA) has relatively low sensitivity for early-stage disease. Morbidity in arthritis could be markedly decreased if early-stag...
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description | There is currently no blood-based test for detection of early-stage osteoarthritis (OA) and the anti-cyclic citrullinated peptide (CCP) antibody test for rheumatoid arthritis (RA) has relatively low sensitivity for early-stage disease. Morbidity in arthritis could be markedly decreased if early-stage arthritis could be routinely detected and classified by clinical chemistry test. We hypothesised that damage to proteins of the joint by oxidation, nitration and glycation, and with signatures released in plasma as oxidized, nitrated and glycated amino acids may facilitate early-stage diagnosis and typing of arthritis.
Patients with knee joint early-stage and advanced OA and RA or other inflammatory joint disease (non-RA) and healthy subjects with good skeletal health were recruited for the study (n = 225). Plasma/serum and synovial fluid was analysed for oxidized, nitrated and glycated proteins and amino acids by quantitative liquid chromatography-tandem mass spectrometry. Data-driven machine learning methods were employed to explore diagnostic utility of the measurements for detection and classifying early-stage OA and RA, non-RA and good skeletal health with training set and independent test set cohorts.
Glycated, oxidized and nitrated proteins and amino acids were detected in synovial fluid and plasma of arthritic patients with characteristic patterns found in early and advanced OA and RA, and non-RA, with respect to healthy controls. In early-stage disease, two algorithms for consecutive use in diagnosis were developed: (1) disease versus healthy control, and (2) classification as OA, RA and non-RA. The algorithms featured 10 damaged amino acids in plasma, hydroxyproline and anti-CCP antibody status. Sensitivities/specificities were: (1) good skeletal health, 0.92/0.91; (2) early-stage OA, 0.92/0.90; early-stage RA, 0.80/0.78; and non-RA, 0.70/0.65 (training set). These were confirmed in independent test set validation. Damaged amino acids increased further in severe and advanced OA and RA.
Oxidized, nitrated and glycated amino acids combined with hydroxyproline and anti-CCP antibody status provided a plasma-based biochemical test of relatively high sensitivity and specificity for early-stage diagnosis and typing of arthritic disease. |
doi_str_mv | 10.1186/s13075-016-1154-3 |
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Patients with knee joint early-stage and advanced OA and RA or other inflammatory joint disease (non-RA) and healthy subjects with good skeletal health were recruited for the study (n = 225). Plasma/serum and synovial fluid was analysed for oxidized, nitrated and glycated proteins and amino acids by quantitative liquid chromatography-tandem mass spectrometry. Data-driven machine learning methods were employed to explore diagnostic utility of the measurements for detection and classifying early-stage OA and RA, non-RA and good skeletal health with training set and independent test set cohorts.
Glycated, oxidized and nitrated proteins and amino acids were detected in synovial fluid and plasma of arthritic patients with characteristic patterns found in early and advanced OA and RA, and non-RA, with respect to healthy controls. In early-stage disease, two algorithms for consecutive use in diagnosis were developed: (1) disease versus healthy control, and (2) classification as OA, RA and non-RA. The algorithms featured 10 damaged amino acids in plasma, hydroxyproline and anti-CCP antibody status. Sensitivities/specificities were: (1) good skeletal health, 0.92/0.91; (2) early-stage OA, 0.92/0.90; early-stage RA, 0.80/0.78; and non-RA, 0.70/0.65 (training set). These were confirmed in independent test set validation. Damaged amino acids increased further in severe and advanced OA and RA.
Oxidized, nitrated and glycated amino acids combined with hydroxyproline and anti-CCP antibody status provided a plasma-based biochemical test of relatively high sensitivity and specificity for early-stage diagnosis and typing of arthritic disease.</description><identifier>ISSN: 1478-6362</identifier><identifier>ISSN: 1478-6354</identifier><identifier>EISSN: 1478-6362</identifier><identifier>DOI: 10.1186/s13075-016-1154-3</identifier><identifier>PMID: 27788684</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adult ; Aged ; Algorithms ; Amino Acids - metabolism ; Area Under Curve ; Arthritis ; Biological markers ; Biomarkers - blood ; Chromatography, Liquid ; Development and progression ; Diagnosis ; Disease Progression ; Early Diagnosis ; Female ; Genetic aspects ; Humans ; Male ; Middle Aged ; Nitrosation ; Osteoarthritis ; Osteoarthritis, Knee - blood ; Osteoarthritis, Knee - diagnosis ; Oxidation-Reduction ; Oxidative Stress ; Physiological aspects ; Protein Processing, Post-Translational ; ROC Curve ; Sensitivity and Specificity ; Tandem Mass Spectrometry</subject><ispartof>Arthritis research & therapy, 2016-10, Vol.18 (1), p.250-250, Article 250</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2016</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-c397f1812d184d63ac811e4e9b5632581c735cac4353f58b9114f9c88c982c943</citedby><cites>FETCH-LOGICAL-c494t-c397f1812d184d63ac811e4e9b5632581c735cac4353f58b9114f9c88c982c943</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/PMC5081671/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081671/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27788684$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahmed, Usman</creatorcontrib><creatorcontrib>Anwar, Attia</creatorcontrib><creatorcontrib>Savage, Richard S</creatorcontrib><creatorcontrib>Thornalley, Paul J</creatorcontrib><creatorcontrib>Rabbani, Naila</creatorcontrib><title>Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease</title><title>Arthritis research & therapy</title><addtitle>Arthritis Res Ther</addtitle><description>There is currently no blood-based test for detection of early-stage osteoarthritis (OA) and the anti-cyclic citrullinated peptide (CCP) antibody test for rheumatoid arthritis (RA) has relatively low sensitivity for early-stage disease. Morbidity in arthritis could be markedly decreased if early-stage arthritis could be routinely detected and classified by clinical chemistry test. We hypothesised that damage to proteins of the joint by oxidation, nitration and glycation, and with signatures released in plasma as oxidized, nitrated and glycated amino acids may facilitate early-stage diagnosis and typing of arthritis.
Patients with knee joint early-stage and advanced OA and RA or other inflammatory joint disease (non-RA) and healthy subjects with good skeletal health were recruited for the study (n = 225). Plasma/serum and synovial fluid was analysed for oxidized, nitrated and glycated proteins and amino acids by quantitative liquid chromatography-tandem mass spectrometry. Data-driven machine learning methods were employed to explore diagnostic utility of the measurements for detection and classifying early-stage OA and RA, non-RA and good skeletal health with training set and independent test set cohorts.
Glycated, oxidized and nitrated proteins and amino acids were detected in synovial fluid and plasma of arthritic patients with characteristic patterns found in early and advanced OA and RA, and non-RA, with respect to healthy controls. In early-stage disease, two algorithms for consecutive use in diagnosis were developed: (1) disease versus healthy control, and (2) classification as OA, RA and non-RA. The algorithms featured 10 damaged amino acids in plasma, hydroxyproline and anti-CCP antibody status. Sensitivities/specificities were: (1) good skeletal health, 0.92/0.91; (2) early-stage OA, 0.92/0.90; early-stage RA, 0.80/0.78; and non-RA, 0.70/0.65 (training set). These were confirmed in independent test set validation. Damaged amino acids increased further in severe and advanced OA and RA.
Oxidized, nitrated and glycated amino acids combined with hydroxyproline and anti-CCP antibody status provided a plasma-based biochemical test of relatively high sensitivity and specificity for early-stage diagnosis and typing of arthritic disease.</description><subject>Adult</subject><subject>Aged</subject><subject>Algorithms</subject><subject>Amino Acids - metabolism</subject><subject>Area Under Curve</subject><subject>Arthritis</subject><subject>Biological markers</subject><subject>Biomarkers - blood</subject><subject>Chromatography, Liquid</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Disease Progression</subject><subject>Early Diagnosis</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nitrosation</subject><subject>Osteoarthritis</subject><subject>Osteoarthritis, Knee - blood</subject><subject>Osteoarthritis, Knee - diagnosis</subject><subject>Oxidation-Reduction</subject><subject>Oxidative Stress</subject><subject>Physiological aspects</subject><subject>Protein Processing, Post-Translational</subject><subject>ROC Curve</subject><subject>Sensitivity and Specificity</subject><subject>Tandem Mass Spectrometry</subject><issn>1478-6362</issn><issn>1478-6354</issn><issn>1478-6362</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNptks1u1DAUhSMEoqXwAGyQJTYsSMn1X5wNUlXxJ1WCBawtj3OTcZuxB9tTMQ_Du-JM2tIi5IWvr8_5rGudqnoJzSmAku8SsKYVdQOyBhC8Zo-qY-CtqiWT9PG9-qh6ltJl01DaUf60OqJtq5RU_Lj6_S2GjM6T8Mv1Jrvg3xLvcjyUxPiejNPeLqeVCxsTrzAmMoRI0MRpX6dsRiS9M6MPySUSBhJSxmBiXkeXl05eI7nyiAdg3m-dHw_lNoYxYkozvchuPbbwEpqEz6sng5kSvrjZT6ofHz98P_9cX3z99OX87KK2vOO5tqxrB1BAe1C8l8xYBYAcu5WQjAoFtmXCGsuZYINQqw6AD51VynaK2o6zk-r9wt3uVhvsLfryA5PeRlcG3utgnH54491aj-Fai0aBbKEA3twAYvi5w5T1xiWL02Q8hl3SoJgQlEs-S1__I70Mu-jLeLNKCtk2bfdXNZoJtfNDKO_aGarPuFRl2AIsqtP_qMrqceNs8Di40n9ggMVgY0gp4nA3IzR6zpReMqVLpvScKc2K59X9z7lz3IaI_QHFRMm1</recordid><startdate>20161027</startdate><enddate>20161027</enddate><creator>Ahmed, Usman</creator><creator>Anwar, Attia</creator><creator>Savage, Richard S</creator><creator>Thornalley, Paul J</creator><creator>Rabbani, Naila</creator><general>BioMed Central Ltd</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161027</creationdate><title>Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease</title><author>Ahmed, Usman ; Anwar, Attia ; Savage, Richard S ; Thornalley, Paul J ; Rabbani, Naila</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-c397f1812d184d63ac811e4e9b5632581c735cac4353f58b9114f9c88c982c943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Algorithms</topic><topic>Amino Acids - metabolism</topic><topic>Area Under Curve</topic><topic>Arthritis</topic><topic>Biological markers</topic><topic>Biomarkers - blood</topic><topic>Chromatography, Liquid</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Disease Progression</topic><topic>Early Diagnosis</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nitrosation</topic><topic>Osteoarthritis</topic><topic>Osteoarthritis, Knee - blood</topic><topic>Osteoarthritis, Knee - diagnosis</topic><topic>Oxidation-Reduction</topic><topic>Oxidative Stress</topic><topic>Physiological aspects</topic><topic>Protein Processing, Post-Translational</topic><topic>ROC Curve</topic><topic>Sensitivity and Specificity</topic><topic>Tandem Mass Spectrometry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahmed, Usman</creatorcontrib><creatorcontrib>Anwar, Attia</creatorcontrib><creatorcontrib>Savage, Richard S</creatorcontrib><creatorcontrib>Thornalley, Paul J</creatorcontrib><creatorcontrib>Rabbani, Naila</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</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>Ahmed, Usman</au><au>Anwar, Attia</au><au>Savage, Richard S</au><au>Thornalley, Paul J</au><au>Rabbani, Naila</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease</atitle><jtitle>Arthritis research & therapy</jtitle><addtitle>Arthritis Res Ther</addtitle><date>2016-10-27</date><risdate>2016</risdate><volume>18</volume><issue>1</issue><spage>250</spage><epage>250</epage><pages>250-250</pages><artnum>250</artnum><issn>1478-6362</issn><issn>1478-6354</issn><eissn>1478-6362</eissn><abstract>There is currently no blood-based test for detection of early-stage osteoarthritis (OA) and the anti-cyclic citrullinated peptide (CCP) antibody test for rheumatoid arthritis (RA) has relatively low sensitivity for early-stage disease. Morbidity in arthritis could be markedly decreased if early-stage arthritis could be routinely detected and classified by clinical chemistry test. We hypothesised that damage to proteins of the joint by oxidation, nitration and glycation, and with signatures released in plasma as oxidized, nitrated and glycated amino acids may facilitate early-stage diagnosis and typing of arthritis.
Patients with knee joint early-stage and advanced OA and RA or other inflammatory joint disease (non-RA) and healthy subjects with good skeletal health were recruited for the study (n = 225). Plasma/serum and synovial fluid was analysed for oxidized, nitrated and glycated proteins and amino acids by quantitative liquid chromatography-tandem mass spectrometry. Data-driven machine learning methods were employed to explore diagnostic utility of the measurements for detection and classifying early-stage OA and RA, non-RA and good skeletal health with training set and independent test set cohorts.
Glycated, oxidized and nitrated proteins and amino acids were detected in synovial fluid and plasma of arthritic patients with characteristic patterns found in early and advanced OA and RA, and non-RA, with respect to healthy controls. In early-stage disease, two algorithms for consecutive use in diagnosis were developed: (1) disease versus healthy control, and (2) classification as OA, RA and non-RA. The algorithms featured 10 damaged amino acids in plasma, hydroxyproline and anti-CCP antibody status. Sensitivities/specificities were: (1) good skeletal health, 0.92/0.91; (2) early-stage OA, 0.92/0.90; early-stage RA, 0.80/0.78; and non-RA, 0.70/0.65 (training set). These were confirmed in independent test set validation. Damaged amino acids increased further in severe and advanced OA and RA.
Oxidized, nitrated and glycated amino acids combined with hydroxyproline and anti-CCP antibody status provided a plasma-based biochemical test of relatively high sensitivity and specificity for early-stage diagnosis and typing of arthritic disease.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27788684</pmid><doi>10.1186/s13075-016-1154-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Algorithms Amino Acids - metabolism Area Under Curve Arthritis Biological markers Biomarkers - blood Chromatography, Liquid Development and progression Diagnosis Disease Progression Early Diagnosis Female Genetic aspects Humans Male Middle Aged Nitrosation Osteoarthritis Osteoarthritis, Knee - blood Osteoarthritis, Knee - diagnosis Oxidation-Reduction Oxidative Stress Physiological aspects Protein Processing, Post-Translational ROC Curve Sensitivity and Specificity Tandem Mass Spectrometry |
title | Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease |
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