{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE269nnn/GSE269658/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269658"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Immune Checkpoint Molecules as Biomarkers of Outcomes in Staphylococcus aureus Bone Infections","description":"Staphylococcus aureus prosthetic joint infections (PJIs) are considered incurable. Unfortunately, clinical diagnostics to guide conservative vs. aggressive surgical treatment of PJI patients are not evidence-based. Developing clinical biomarkers are crucial for defining immunopathogenesis of PJIs. PJI in humanized mice is characterized by increased infection, bone osteolysis, and large numbers of proliferating CD3+/Tbet+ cells adjacent to purulent abscesses in the bone marrow. Multi-omics studies in a humanized NSG-SGM3 BLT PJI mouse indicated the role of human T cells where 1) human T cells are remarkably heterogenous in gene expression and numbers, 2) human Th1/Th17 exists as a mixed population of activated, progenitor-exhausted, and terminally-exhausted cells which exhibit increased expression of immune checkpoint proteins (LAG3, TIM-3) 2-weeks post-infection. Moreover, 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 (IFN-g, IL-2, TNF-α, IL-17) revealed that TIM-3 was highly predictive of adverse outcomes in PJI patients (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 checkpoint blockade may benefit PJI patients.","dates":{"publication":"2026/06/30"},"accession":"GSE269658","cross_references":{"GSM":["GSM8324292","GSM8324291","GSM8324294","GSM8324293","GSM8324290","GSM8324300","GSM8324289","GSM8324299","GSM8324288","GSM8324302","GSM8324301","GSM8324296","GSM8324285","GSM8324295","GSM8324287","GSM8324298","GSM8324297","GSM8324286"],"GPL":["24676"],"GSE":["269658"],"taxon":["Homo sapiens"]}}