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Synovial fluid monocyte/macrophage subsets and their correlation to patient-reported outcomes in osteoarthritic patients: a cohort study

Background Chronic, low-grade inflammation of the synovium (synovitis) is a hallmark of osteoarthritis (OA), thus understanding of OA immunobiology, mediated by immune effectors, is of importance. Specifically, monocytes/macrophages (MΦs) are known to be abundantly present in OA joints and involved...

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Published in:Arthritis Research & Therapy 2019, Vol.21 (1)
Main Authors: Gómez-Aristizábal, Alejandro, Gandhi, Rajiv, Mahomed, Nizar N, Marshall, K. Wayne, Viswanathan, Sowmya
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container_title Arthritis Research & Therapy
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Gandhi, Rajiv
Mahomed, Nizar N
Marshall, K. Wayne
Viswanathan, Sowmya
description Background Chronic, low-grade inflammation of the synovium (synovitis) is a hallmark of osteoarthritis (OA), thus understanding of OA immunobiology, mediated by immune effectors, is of importance. Specifically, monocytes/macrophages (MΦs) are known to be abundantly present in OA joints and involved in OA progression. However, different subsets of OA MΦs have not been investigated in detail, especially in terms of their relationship with patient-reported outcome measures (PROMs). We hypothesized that levels of synovial fluid (SF) MΦ subsets are indicative of joint function and quality of life in patients with OA, and can therefore serve as biomarkers and therapeutic targets for OA. Methods In this cohort study, synovial fluid leukocytes (SFLs, N = 86) and peripheral blood mononuclear cells (n = 53) from patients with knee OA were characterized. Soluble MΦ receptors and chemokine (sCD14, sCD163, CCL2, CX3CL1) levels were detected in SF using immunoassays. Linear models, adjusted for sex, age and body mass index, were used to determine associations between SF MΦs and soluble factors with PROMs (N = 83). Pearson correlation was calculated to determine correlation between MΦ subsets, T cells and soluble factors. Results SF MΦs were the most abundant SFLs. Within these, the double-positive CD14.sup.+CD16.sup.+-MΦ subset is enriched in knee OA SF compared to the circulation. Importantly, MΦ subset ratios correlated with PROMs, specially stiffness, function and quality of life. Interestingly, the SF CD14.sup.+CD16.sup.+-MΦ subset ratio correlated with SF chemokine (C-C motif) ligand 2 (CCL2) levels but not with levels of sCD163 or sCD14; we found no association between PROMs and either SF CCL2, sCD163, sCD14 or CX3CL1 (which was below detection levels). All SF MΦs displayed high levels of HLA-DR, suggesting an activated phenotype. Correlation between OA SF MΦ subsets and activated CD4.sup.+ T cell subsets suggests modulation of CD4.sup.+ T cell activation by MΦs. Conclusion SF MΦ subsets are associated with knee OA PROMs and display an activated phenotype, which may lead to modulation of CD4.sup.+ T cell activation. Knee OA SF MΦ subsets could serve as knee OA function biomarkers and as targets of novel therapeutics. Keywords: Osteoarthritis, Synovial fluid, Monocytes/macrophages, PROMs, Leukocytes
doi_str_mv 10.1186/s13075-018-1798-2
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Wayne ; Viswanathan, Sowmya</creator><creatorcontrib>Gómez-Aristizábal, Alejandro ; Gandhi, Rajiv ; Mahomed, Nizar N ; Marshall, K. Wayne ; Viswanathan, Sowmya</creatorcontrib><description>Background Chronic, low-grade inflammation of the synovium (synovitis) is a hallmark of osteoarthritis (OA), thus understanding of OA immunobiology, mediated by immune effectors, is of importance. Specifically, monocytes/macrophages (MΦs) are known to be abundantly present in OA joints and involved in OA progression. However, different subsets of OA MΦs have not been investigated in detail, especially in terms of their relationship with patient-reported outcome measures (PROMs). We hypothesized that levels of synovial fluid (SF) MΦ subsets are indicative of joint function and quality of life in patients with OA, and can therefore serve as biomarkers and therapeutic targets for OA. Methods In this cohort study, synovial fluid leukocytes (SFLs, N = 86) and peripheral blood mononuclear cells (n = 53) from patients with knee OA were characterized. Soluble MΦ receptors and chemokine (sCD14, sCD163, CCL2, CX3CL1) levels were detected in SF using immunoassays. Linear models, adjusted for sex, age and body mass index, were used to determine associations between SF MΦs and soluble factors with PROMs (N = 83). Pearson correlation was calculated to determine correlation between MΦ subsets, T cells and soluble factors. Results SF MΦs were the most abundant SFLs. Within these, the double-positive CD14.sup.+CD16.sup.+-MΦ subset is enriched in knee OA SF compared to the circulation. Importantly, MΦ subset ratios correlated with PROMs, specially stiffness, function and quality of life. Interestingly, the SF CD14.sup.+CD16.sup.+-MΦ subset ratio correlated with SF chemokine (C-C motif) ligand 2 (CCL2) levels but not with levels of sCD163 or sCD14; we found no association between PROMs and either SF CCL2, sCD163, sCD14 or CX3CL1 (which was below detection levels). All SF MΦs displayed high levels of HLA-DR, suggesting an activated phenotype. Correlation between OA SF MΦ subsets and activated CD4.sup.+ T cell subsets suggests modulation of CD4.sup.+ T cell activation by MΦs. Conclusion SF MΦ subsets are associated with knee OA PROMs and display an activated phenotype, which may lead to modulation of CD4.sup.+ T cell activation. Knee OA SF MΦ subsets could serve as knee OA function biomarkers and as targets of novel therapeutics. 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Wayne</creatorcontrib><creatorcontrib>Viswanathan, Sowmya</creatorcontrib><title>Synovial fluid monocyte/macrophage subsets and their correlation to patient-reported outcomes in osteoarthritic patients: a cohort study</title><title>Arthritis Research &amp; Therapy</title><description>Background Chronic, low-grade inflammation of the synovium (synovitis) is a hallmark of osteoarthritis (OA), thus understanding of OA immunobiology, mediated by immune effectors, is of importance. Specifically, monocytes/macrophages (MΦs) are known to be abundantly present in OA joints and involved in OA progression. However, different subsets of OA MΦs have not been investigated in detail, especially in terms of their relationship with patient-reported outcome measures (PROMs). We hypothesized that levels of synovial fluid (SF) MΦ subsets are indicative of joint function and quality of life in patients with OA, and can therefore serve as biomarkers and therapeutic targets for OA. Methods In this cohort study, synovial fluid leukocytes (SFLs, N = 86) and peripheral blood mononuclear cells (n = 53) from patients with knee OA were characterized. Soluble MΦ receptors and chemokine (sCD14, sCD163, CCL2, CX3CL1) levels were detected in SF using immunoassays. Linear models, adjusted for sex, age and body mass index, were used to determine associations between SF MΦs and soluble factors with PROMs (N = 83). Pearson correlation was calculated to determine correlation between MΦ subsets, T cells and soluble factors. Results SF MΦs were the most abundant SFLs. Within these, the double-positive CD14.sup.+CD16.sup.+-MΦ subset is enriched in knee OA SF compared to the circulation. Importantly, MΦ subset ratios correlated with PROMs, specially stiffness, function and quality of life. Interestingly, the SF CD14.sup.+CD16.sup.+-MΦ subset ratio correlated with SF chemokine (C-C motif) ligand 2 (CCL2) levels but not with levels of sCD163 or sCD14; we found no association between PROMs and either SF CCL2, sCD163, sCD14 or CX3CL1 (which was below detection levels). All SF MΦs displayed high levels of HLA-DR, suggesting an activated phenotype. Correlation between OA SF MΦ subsets and activated CD4.sup.+ T cell subsets suggests modulation of CD4.sup.+ T cell activation by MΦs. Conclusion SF MΦ subsets are associated with knee OA PROMs and display an activated phenotype, which may lead to modulation of CD4.sup.+ T cell activation. Knee OA SF MΦ subsets could serve as knee OA function biomarkers and as targets of novel therapeutics. 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Wayne</creator><creator>Viswanathan, Sowmya</creator><general>BioMed Central Ltd</general><scope/></search><sort><creationdate>20190118</creationdate><title>Synovial fluid monocyte/macrophage subsets and their correlation to patient-reported outcomes in osteoarthritic patients: a cohort study</title><author>Gómez-Aristizábal, Alejandro ; Gandhi, Rajiv ; Mahomed, Nizar N ; Marshall, K. Wayne ; Viswanathan, Sowmya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-gale_infotracacademiconefile_A5814188003</frbrgroupid><rsrctype>reports</rsrctype><prefilter>reports</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Analysis</topic><topic>Biological markers</topic><topic>Care and treatment</topic><topic>Displays (Marketing)</topic><topic>Fc receptors</topic><topic>Inflammation</topic><topic>Medical research</topic><topic>Novels</topic><topic>Osteoarthritis</topic><topic>Prognosis</topic><topic>Proms (Parties)</topic><topic>Synovial fluid analysis</topic><topic>Synovitis</topic><topic>T cells</topic><topic>Therapeutics</topic><toplevel>online_resources</toplevel><creatorcontrib>Gómez-Aristizábal, Alejandro</creatorcontrib><creatorcontrib>Gandhi, Rajiv</creatorcontrib><creatorcontrib>Mahomed, Nizar N</creatorcontrib><creatorcontrib>Marshall, K. Wayne</creatorcontrib><creatorcontrib>Viswanathan, Sowmya</creatorcontrib></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gómez-Aristizábal, Alejandro</au><au>Gandhi, Rajiv</au><au>Mahomed, Nizar N</au><au>Marshall, K. Wayne</au><au>Viswanathan, Sowmya</au><format>book</format><genre>unknown</genre><ristype>RPRT</ristype><atitle>Synovial fluid monocyte/macrophage subsets and their correlation to patient-reported outcomes in osteoarthritic patients: a cohort study</atitle><jtitle>Arthritis Research &amp; Therapy</jtitle><date>2019-01-18</date><risdate>2019</risdate><volume>21</volume><issue>1</issue><issn>1478-6354</issn><abstract>Background Chronic, low-grade inflammation of the synovium (synovitis) is a hallmark of osteoarthritis (OA), thus understanding of OA immunobiology, mediated by immune effectors, is of importance. Specifically, monocytes/macrophages (MΦs) are known to be abundantly present in OA joints and involved in OA progression. However, different subsets of OA MΦs have not been investigated in detail, especially in terms of their relationship with patient-reported outcome measures (PROMs). We hypothesized that levels of synovial fluid (SF) MΦ subsets are indicative of joint function and quality of life in patients with OA, and can therefore serve as biomarkers and therapeutic targets for OA. Methods In this cohort study, synovial fluid leukocytes (SFLs, N = 86) and peripheral blood mononuclear cells (n = 53) from patients with knee OA were characterized. Soluble MΦ receptors and chemokine (sCD14, sCD163, CCL2, CX3CL1) levels were detected in SF using immunoassays. Linear models, adjusted for sex, age and body mass index, were used to determine associations between SF MΦs and soluble factors with PROMs (N = 83). Pearson correlation was calculated to determine correlation between MΦ subsets, T cells and soluble factors. Results SF MΦs were the most abundant SFLs. Within these, the double-positive CD14.sup.+CD16.sup.+-MΦ subset is enriched in knee OA SF compared to the circulation. Importantly, MΦ subset ratios correlated with PROMs, specially stiffness, function and quality of life. Interestingly, the SF CD14.sup.+CD16.sup.+-MΦ subset ratio correlated with SF chemokine (C-C motif) ligand 2 (CCL2) levels but not with levels of sCD163 or sCD14; we found no association between PROMs and either SF CCL2, sCD163, sCD14 or CX3CL1 (which was below detection levels). All SF MΦs displayed high levels of HLA-DR, suggesting an activated phenotype. Correlation between OA SF MΦ subsets and activated CD4.sup.+ T cell subsets suggests modulation of CD4.sup.+ T cell activation by MΦs. Conclusion SF MΦ subsets are associated with knee OA PROMs and display an activated phenotype, which may lead to modulation of CD4.sup.+ T cell activation. Knee OA SF MΦ subsets could serve as knee OA function biomarkers and as targets of novel therapeutics. Keywords: Osteoarthritis, Synovial fluid, Monocytes/macrophages, PROMs, Leukocytes</abstract><pub>BioMed Central Ltd</pub><doi>10.1186/s13075-018-1798-2</doi></addata></record>
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subjects Analysis
Biological markers
Care and treatment
Displays (Marketing)
Fc receptors
Inflammation
Medical research
Novels
Osteoarthritis
Prognosis
Proms (Parties)
Synovial fluid analysis
Synovitis
T cells
Therapeutics
title Synovial fluid monocyte/macrophage subsets and their correlation to patient-reported outcomes in osteoarthritic patients: a cohort study
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