{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T10:05:24Z","timestamp":1780394724172,"version":"3.54.1"},"reference-count":0,"publisher":"Knowledge Enterprise Journals","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MRAJ"],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:p>Staphylococcus aureus prosthetic joint infection (PJI) is notoriously difficult to treat and is often associated with septic death. Results from the V710 Phase IIB\/III clinical trial and subsequent research have demonstrated that non-neutralizing antibodies against the iron-regulated surface determinant protein B (IsdB) facilitate bacterial entry into leukocytes, generating \"Trojan horse\" leukocytes and the dissemination of surgical-site infections. In contrast, anti-glucosaminidase (Gmd) antibodies, which mediate opsonophagocytosis of bacterial clusters, are associated with protection from S. aureus osteomyelitis in both mice and humans. To further test whether anti-IsdB antibodies are pathogenic and anti-Gmd antibodies are protective in PJI patients, we performed a clinical pilot study of three healthy patients undergoing primary total hip arthroplasty (THA) and a patient undergoing revision THA for S. aureus PJI to assess the feasibility of quantifying anti-IsdB and anti-Gmd antibody-secreting cells in blood and periprosthetic bone marrow. We also assessed anti-IsdB and anti-Gmd antibody levels in serum, blood plasma, bone marrow plasma, and cell culture supernatant collected after six days with and without a previously established memory B-cell (MBC) stimulation cocktail. The frequencies of MBC and antibody-secreting plasmablasts were measured using IgG ELISpot. Consistent with our hypothesis, we found large numbers of anti-IsdB antibody-secreting cells in unstimulated periprosthetic bone marrow from the PJI patient, which increased with stimulation. However, these cells were only detectable in peripheral blood mononuclear cells following stimulation. Furthermore, anti-Gmd antibody-secreting cells were undetectable in the bone marrow of this PJI patient at the time of revision surgery. This patient also had very high titers of anti-IsdB antibodies in serum, blood plasma, and bone marrow plasma. Anti-IsdB and anti-Gmd antibody-secreting cells were only detected in bone marrow for one of the uninfected patients. Collectively, the results are consistent with the hypothesis that anti-IsdB antibodies are associated with disease and related to the presence of IsdB-specific MBC and plasmablasts. These case reports demonstrate the utility of ELISpot to assess local vs. systemic antigen-specific humoral responses in THA patients and support a larger study to test the hypothesis that anti-IsdB antibody-secreting cells proximal to S. aureus infected implants are associated with recalcitrant infections and septic death.<\/jats:p>","DOI":"10.18103\/mra.v14i1.7191","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T13:28:06Z","timestamp":1770125286000},"source":"Crossref","is-referenced-by-count":1,"title":["ELISpot detection of anti-IsdB antibody-secreting cells in S. aureus infected bone marrow: Case Reports of Total Hip Arthroplasty Patients"],"prefix":"10.18103","volume":"14","author":[{"given":"Edward","family":"Schwarz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gowrishankar","family":"Muthukrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Topham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Daiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Kates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7483","published-online":{"date-parts":[[2025]]},"container-title":["Medical Research Archives"],"original-title":[],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T13:28:07Z","timestamp":1770125287000},"score":1,"resource":{"primary":{"URL":"https:\/\/esmed.org\/MRA\/mra\/article\/view\/7191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025]]},"published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.18103\/mra.v14i1.7191","relation":{},"ISSN":["2375-1916","2375-1924"],"issn-type":[{"value":"2375-1916","type":"print"},{"value":"2375-1924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]}}}