{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:05:58Z","timestamp":1787763958206,"version":"build-2784847793"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,2,5]],"date-time":"2022-02-05T00:00:00Z","timestamp":1644019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Periprosthetic joint infections (PJI) induce an immunosuppressive cytokine profile through an unknown mechanism. Immune checkpoints, like programmed cell death 1 (PD\u20101) and its ligand (PD\u2010L1), initiate innate immunosuppressive pathways essential for self\u2010tolerance. Several malignancies and chronic infections co\u2010opt these pathways to derive a survival advantage. This study evaluates PD\u20101\/PD\u2010L1 expression in periprosthetic tissue from patients undergoing revision hip or knee arthroplasty for a PJI versus an aseptic failure. PD\u20101\/PD\u2010L1 in the global tissue sample and the high\u2010power microscopic field of maximum expression was analyzed prospectively using immunohistochemistry. Fifteen patients with a PJI (45%) and 16 patients with an aseptic failure (52%) were included. PD\u20101 expression was uniformly low. Maximum PD\u2010L1 expression was upregulated in patients with a PJI (25%, interquartile range [IQR]: 5%\u201375%) versus an aseptic failure, (8%, IQR: 1%\u201348%, <jats:italic>p<\/jats:italic>\u2009=\u20090.039). In the PJI cohort, maximum PD\u2010L1 expression was higher among patients who developed a recurrent PJI (68%, IQR: 53%\u201386% vs. 15%, IQR: 5%\u201370%, <jats:italic>p<\/jats:italic>\u2009=\u20090.039). Patients with global PD\u2010L1 over 5% trended toward a near 22\u2010fold increase in the odds of reinfection (odds ratio [OR]: 21.9, 95% confidence interval [CI]: 0.9\u2013523.5, <jats:italic>p<\/jats:italic>\u2009=\u20090.057) and patients with maximum PD\u2010L1 over 20% trended toward a 15\u2010fold increase in the odds of reinfection (OR: 15.0, 95% CI: 0.6\u2013348.9, <jats:italic>p<\/jats:italic>\u2009=\u20090.092). These results support immune checkpoint upregulation as a mechanism of PJI\u2010induced local immune dysfunction. Future studies should confirm PD\u2010L1 as a risk factor for reinfection in larger cohorts.<\/jats:p>","DOI":"10.1002\/jor.25276","type":"journal-article","created":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T05:34:00Z","timestamp":1644125640000},"page":"2663-2669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immune checkpoint upregulation in periprosthetic joint infection"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1272-7093","authenticated-orcid":false,"given":"Shay I.","family":"Warren","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Stanford University Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2774-2704","authenticated-orcid":false,"given":"Gregory W.","family":"Charville","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3236-789X","authenticated-orcid":false,"given":"Robert","family":"Manasherob","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Stanford University Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6203-5853","authenticated-orcid":false,"given":"Derek F.","family":"Amanatullah","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Stanford University Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2015.03.035"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00111-13"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1302\/2058-5241.4.190003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.91B11.22026"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2006.02.156"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-013-3294-y"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.L.00789"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115611"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2326"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.112"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000515"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000006369"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.06.001"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2180"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07662"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.09.052"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix191"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.028"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx696"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183271"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23806"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002794"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4VMA0315-125RR"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-015-5022-7"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2018.02.078"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80011"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.091101.091806"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-019-0955-2"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.OA.17.00060"},{"issue":"1","key":"e_1_2_7_31_1","first-page":"S136","article-title":"Antibiotic treatment and timing of reimplantation","volume":"32","author":"Restrepo C","year":"2014","journal-title":"J Orthop Res"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00606"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v030a22"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25276","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.25276","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25276","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T16:18:57Z","timestamp":1692548337000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.25276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,5]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/jor.25276"],"URL":"https:\/\/doi.org\/10.1002\/jor.25276","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,5]]},"assertion":[{"value":"2021-09-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}