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dc.contributor.authorRitter, Susan Yen_US
dc.contributor.authorCollins, Jamieen_US
dc.contributor.authorKrastins, Bryanen_US
dc.contributor.authorSarracino, Daviden_US
dc.contributor.authorLopez, Maryen_US
dc.contributor.authorLosina, Elenaen_US
dc.contributor.authorAliprantis, Antonios Oen_US
dc.date.accessioned2014-11-03T17:40:14Z
dc.date.issued2014en_US
dc.identifier.citationRitter, Susan Y, Jamie Collins, Bryan Krastins, David Sarracino, Mary Lopez, Elena Losina, and Antonios O Aliprantis. 2014. “Mass spectrometry assays of plasma biomarkers to predict radiographic progression of knee osteoarthritis.” Arthritis Research & Therapy 16 (5): 456. doi:10.1186/s13075-014-0456-6. http://dx.doi.org/10.1186/s13075-014-0456-6.en
dc.identifier.issn1478-6354en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13347590
dc.description.abstractIntroduction: Biomarkers to identify osteoarthritis (OA) patients at risk for disease progression are needed. As part of a proteomic analysis of knee synovial fluid from normal and OA patients, differentially expressed proteins were identified that could represent potential biomarkers for OA. This study aimed to use mass spectrometry assays to identify representative peptides from several proteins in synovial fluid and peripheral blood, and assess their levels as biomarkers of OA progression. Methods: Multiplexed high throughput selected reaction monitoring (SRM) assays were developed to measure tryptic peptides representative of 23 proteins in matched serum and synovial fluid samples from late OA subjects at the time of joint replacement. Subsequently plasma samples from the baseline visit of 173 subjects in an observational OA cohort were tested by SRM for peptides from nine of these proteins: afamin, clusterin, cartilage oligomeric matrix protein, hepatocyte growth factor, kallistatin, insulin-like growth factor binding protein, acid labile subunit, lubricin, lumican, and pigment epithelium-derived factor. Linear regression was used to determine the association between the peptide biomarker level at baseline and change in joint space width (ΔJSW) from baseline to 30 months, adjusting for age and sex. Results: In the matched cohort, 17 proteins could be identified in synovial fluid and 16 proteins were detected in serum. For the progression cohort, the average age was 62 and average ΔJSW over 30 months was 0.68 mm. A high correlation between different peptides from individual proteins was observed, indicating our assays correctly measured their target proteins. Peptides representative of clusterin, lumican and lubricin showed statistically significant associations with joint space narrowing after adjustment for age and sex. Partial R2 values showed clusterin FMETVAEK and lubricin LVEVNPK peptide biomarkers explains about 2 to 3% of the variability of ΔJSW, similar to that explained by age. A biomarker score combining normalized data for both lubricin and clusterin peptides increased the model R2 to 0.079. Conclusions: Our results suggest that when combined, levels of peptides representative of clusterin and lubricin in plasma are as predictive of OA progression as age. Replication of these findings in other prospective OA cohorts is planned. Electronic supplementary material The online version of this article (doi:10.1186/s13075-014-0456-6) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s13075-014-0456-6en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207325/pdf/en
dash.licenseLAAen_US
dc.titleMass spectrometry assays of plasma biomarkers to predict radiographic progression of knee osteoarthritisen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalArthritis Research & Therapyen
dash.depositing.authorRitter, Susan Yen_US
dc.date.available2014-11-03T17:40:14Z
dc.identifier.doi10.1186/s13075-014-0456-6*
dash.contributor.affiliatedRitter, Susan
dash.contributor.affiliatedAliprantis, Antonios
dash.contributor.affiliatedCollins, Jamie
dash.contributor.affiliatedLosina, Elena


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