{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:59:25Z","timestamp":1790553565402,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"Objective<\/jats:title>Ankylosing spondylitis (AS<\/jats:styled-content>) is an inflammatory arthritis in which men have a higher risk of developing progressive axial disease than women. Transcriptomic studies have shown reduced expression of cytotoxic cell genes in the blood of AS<\/jats:styled-content> patients. HLA<\/jats:styled-content>\u2013B27 contributes the greatest risk for AS<\/jats:styled-content>, suggesting a role for CD<\/jats:styled-content>8+ T cells. This study was undertaken to profile AS<\/jats:styled-content> patient cytotoxic cells with the hypothesis that an alteration in CD<\/jats:styled-content>8+ T cells might explain the aberrant cytotoxic profile observed in patients.<\/jats:p><\/jats:sec>Methods<\/jats:title>Whole blood was examined for GZM<\/jats:italic> and PRF1<\/jats:italic> gene expression by quantitative polymerase chain reaction. Serum and synovial fluid (SF<\/jats:styled-content>) were examined for granzyme and perforin 1 expression by bead array, and blood and SF<\/jats:styled-content> mononuclear cells were examined for granzyme and perforin 1 expression by fluorescence\u2010activated cell sorting (FACS<\/jats:styled-content>).<\/jats:p><\/jats:sec>Results<\/jats:title>GZM<\/jats:styled-content><\/jats:italic> and PRF1<\/jats:styled-content><\/jats:italic> gene expression were both reduced in AS<\/jats:styled-content> patients compared to healthy controls, especially in men. Perforin 1, but not granzyme, protein levels were reduced in AS<\/jats:styled-content> patient serum. Granzymes were elevated in AS SF<\/jats:styled-content>, but not in rheumatoid arthritis or osteoarthritis SF<\/jats:styled-content>. FACS<\/jats:styled-content> revealed a reduction in granzyme\u2010positive and perforin 1\u2013positive lymphocytes, but not an intrinsic defect in CD<\/jats:styled-content>8+ T cell granzyme or perforin 1 production. CD<\/jats:styled-content>8+ T cell frequency was reduced in the blood and increased in the SF<\/jats:styled-content> of AS<\/jats:styled-content> patients.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings indicate that AS<\/jats:styled-content> patients have an altered cytotoxic T cell profile. These data suggest that CD<\/jats:styled-content>8+ T cells with a cytotoxic phenotype are recruited to the joints, where they exhibit an activated phenotype. Thus, a central role for CD<\/jats:styled-content>8+ T cells in AS<\/jats:styled-content> may have been overlooked and deserves further study.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41129","type":"journal-article","created":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T03:39:56Z","timestamp":1570678796000},"page":"428-434","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Altered Cytotoxicity Profile of CD<\/scp>8+ T Cells in Ankylosing Spondylitis"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0984-435X","authenticated-orcid":false,"given":"Eric","family":"Gracey","sequence":"first","affiliation":[{"name":"University of Toronto Krembil Research Institute Toronto Western Hospital, and University Health Network Toronto Ontario 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