{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:01:22Z","timestamp":1790013682776,"version":"4.0.1"},"posted":{"date-parts":[[2024,12,31]]},"group-title":"Immunology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,31]]},"abstract":"<jats:p>Staphylococcus aureus prosthetic joint infections (PJIs) are broadly considered incurable, and clinical diagnostics that guide conservative vs. aggressive surgical treatments do not exist. Multi-omics studies in a humanized NSG-SGM3 BLT mouse model demonstrate human T cells: 1) are remarkably heterogenous in gene expression and numbers, and 2) exist as a mixed population of activated, progenitor-exhausted, and terminally-exhausted Th1\/Th17 cells with increased expression of immune checkpoint proteins (LAG3, TIM-3). Importantly, these proteins are upregulated in the serum and the bone marrow of S. aureus PJI patients. A multiparametric nomogram combining high serum immune checkpoint protein levels with low proinflammatory cytokine levels (IFNg, IL-2, TNFa, IL-17) revealed that TIM-3 was highly predictive of adverse disease outcomes (AUC=0.89). Hence, T cell impairment in the form of immune checkpoint expression and exhaustion could be a functional biomarker for S. aureus PJI disease outcome, and blockade of checkpoint proteins could potentially improve outcomes following surgery.<\/jats:p>","DOI":"10.1101\/2024.12.30.630837","type":"posted-content","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T12:52:27Z","timestamp":1735735947000},"source":"Crossref","is-referenced-by-count":4,"title":["Immune Checkpoint Molecules as Biomarkers of Staphylococcus aureus Bone Infection and Clinical Outcome"],"prefix":"10.64898","author":[{"given":"Motoo","family":"Saito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katya A","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander K","family":"Grier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Meghwani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Rangel-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Becerril-Villanueva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Gamboa-Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Proctor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L","family":"Kates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4854-9698","authenticated-orcid":false,"given":"Edward M","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7521-6154","authenticated-orcid":false,"given":"Gowrishankar","family":"Muthukrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.12.30.630837","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:46:29Z","timestamp":1768463189000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.12.30.630837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,31]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2024.12.30.630837","relation":{},"subject":[],"published":{"date-parts":[[2024,12,31]]},"subtype":"preprint"}}