Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries

Background Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joi...

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Veröffentlicht in:Arthritis research & therapy 2021-11, Vol.23 (1), p.1-280, Article 280
Hauptverfasser: Kim-Wang, Sophia Y., Holt, Abigail G., McGowan, Alyssa M., Danyluk, Stephanie T., Goode, Adam P., Lau, Brian C., Toth, Alison P., Wittstein, Jocelyn R., DeFrate, Louis E., Yi, John S., McNulty, Amy L.
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container_end_page 280
container_issue 1
container_start_page 1
container_title Arthritis research & therapy
container_volume 23
creator Kim-Wang, Sophia Y.
Holt, Abigail G.
McGowan, Alyssa M.
Danyluk, Stephanie T.
Goode, Adam P.
Lau, Brian C.
Toth, Alison P.
Wittstein, Jocelyn R.
DeFrate, Louis E.
Yi, John S.
McNulty, Amy L.
description Background Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries. Methods Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects. Results Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type. Conclusions Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.
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Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries. Methods Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects. Results Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type. Conclusions Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.</description><identifier>ISSN: 1478-6354</identifier><identifier>ISSN: 1478-6362</identifier><identifier>EISSN: 1478-6362</identifier><identifier>DOI: 10.1186/s13075-021-02661-1</identifier><identifier>PMID: 34736523</identifier><language>eng</language><publisher>LONDON: Springer Nature</publisher><subject>Age ; Anterior cruciate ligament ; Antibodies ; Arthritis ; B cells ; Biomarkers ; Cartilage ; Chemokines ; Composition ; Cytokines ; Development and progression ; Flow cytometry ; Gene expression ; Health aspects ; Injuries ; Joint and ligament injuries ; Knee ; Life Sciences &amp; Biomedicine ; Lymphocytes ; Macrophages ; Meniscus (Anatomy) ; Monocytes ; Osteoarthritis ; Proteins ; Rheumatology ; Risk factors ; Science &amp; Technology ; Spectrum analysis ; Sports injuries ; Synovial fluid ; T cells ; Tumor necrosis factor-TNF</subject><ispartof>Arthritis research &amp; therapy, 2021-11, Vol.23 (1), p.1-280, Article 280</ispartof><rights>COPYRIGHT 2021 BioMed Central Ltd.</rights><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>13</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000714579200002</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c540t-20c55a5df4c6990c77a42a176eaed8c2bab5f6caba2c3e173e92518282898f9d3</citedby><cites>FETCH-LOGICAL-c540t-20c55a5df4c6990c77a42a176eaed8c2bab5f6caba2c3e173e92518282898f9d3</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/PMC8567695/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567695/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2116,27931,27932,39265,53798,53800</link.rule.ids></links><search><creatorcontrib>Kim-Wang, Sophia Y.</creatorcontrib><creatorcontrib>Holt, Abigail G.</creatorcontrib><creatorcontrib>McGowan, Alyssa M.</creatorcontrib><creatorcontrib>Danyluk, Stephanie T.</creatorcontrib><creatorcontrib>Goode, Adam P.</creatorcontrib><creatorcontrib>Lau, Brian C.</creatorcontrib><creatorcontrib>Toth, Alison P.</creatorcontrib><creatorcontrib>Wittstein, Jocelyn R.</creatorcontrib><creatorcontrib>DeFrate, Louis E.</creatorcontrib><creatorcontrib>Yi, John S.</creatorcontrib><creatorcontrib>McNulty, Amy L.</creatorcontrib><title>Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries</title><title>Arthritis research &amp; therapy</title><addtitle>ARTHRITIS RES THER</addtitle><description>Background Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries. Methods Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects. Results Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type. Conclusions Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.</description><subject>Age</subject><subject>Anterior cruciate ligament</subject><subject>Antibodies</subject><subject>Arthritis</subject><subject>B cells</subject><subject>Biomarkers</subject><subject>Cartilage</subject><subject>Chemokines</subject><subject>Composition</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Health aspects</subject><subject>Injuries</subject><subject>Joint and ligament injuries</subject><subject>Knee</subject><subject>Life Sciences &amp; Biomedicine</subject><subject>Lymphocytes</subject><subject>Macrophages</subject><subject>Meniscus (Anatomy)</subject><subject>Monocytes</subject><subject>Osteoarthritis</subject><subject>Proteins</subject><subject>Rheumatology</subject><subject>Risk factors</subject><subject>Science &amp; 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Holt, Abigail G. ; McGowan, Alyssa M. ; Danyluk, Stephanie T. ; Goode, Adam P. ; Lau, Brian C. ; Toth, Alison P. ; Wittstein, Jocelyn R. ; DeFrate, Louis E. ; Yi, John S. ; McNulty, Amy L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-20c55a5df4c6990c77a42a176eaed8c2bab5f6caba2c3e173e92518282898f9d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Age</topic><topic>Anterior cruciate ligament</topic><topic>Antibodies</topic><topic>Arthritis</topic><topic>B cells</topic><topic>Biomarkers</topic><topic>Cartilage</topic><topic>Chemokines</topic><topic>Composition</topic><topic>Cytokines</topic><topic>Development and progression</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>Health aspects</topic><topic>Injuries</topic><topic>Joint and ligament injuries</topic><topic>Knee</topic><topic>Life Sciences &amp; Biomedicine</topic><topic>Lymphocytes</topic><topic>Macrophages</topic><topic>Meniscus (Anatomy)</topic><topic>Monocytes</topic><topic>Osteoarthritis</topic><topic>Proteins</topic><topic>Rheumatology</topic><topic>Risk factors</topic><topic>Science &amp; 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therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim-Wang, Sophia Y.</au><au>Holt, Abigail G.</au><au>McGowan, Alyssa M.</au><au>Danyluk, Stephanie T.</au><au>Goode, Adam P.</au><au>Lau, Brian C.</au><au>Toth, Alison P.</au><au>Wittstein, Jocelyn R.</au><au>DeFrate, Louis E.</au><au>Yi, John S.</au><au>McNulty, Amy L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries</atitle><jtitle>Arthritis research &amp; therapy</jtitle><stitle>ARTHRITIS RES THER</stitle><date>2021-11-04</date><risdate>2021</risdate><volume>23</volume><issue>1</issue><spage>1</spage><epage>280</epage><pages>1-280</pages><artnum>280</artnum><issn>1478-6354</issn><issn>1478-6362</issn><eissn>1478-6362</eissn><abstract>Background Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries. Methods Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects. Results Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type. Conclusions Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.</abstract><cop>LONDON</cop><pub>Springer Nature</pub><pmid>34736523</pmid><doi>10.1186/s13075-021-02661-1</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Age
Anterior cruciate ligament
Antibodies
Arthritis
B cells
Biomarkers
Cartilage
Chemokines
Composition
Cytokines
Development and progression
Flow cytometry
Gene expression
Health aspects
Injuries
Joint and ligament injuries
Knee
Life Sciences & Biomedicine
Lymphocytes
Macrophages
Meniscus (Anatomy)
Monocytes
Osteoarthritis
Proteins
Rheumatology
Risk factors
Science & Technology
Spectrum analysis
Sports injuries
Synovial fluid
T cells
Tumor necrosis factor-TNF
title Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries
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