{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:42:48Z","timestamp":1790772168244,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"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":["Int J Lab Hematology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The development of anti\u2010factor VIII (FVIII) antibodies or \u201cinhibitors\u201d is a major complication following FVIII replacement therapy in patients with severe hemophilia A (HA), rendering the treatment inefficient. Data on the role of regulatory T cells (Tregs) in inhibitor formation in these patients are rare. Herein, we aimed to investigate whether a difference in the FOXP3<jats:sup>+<\/jats:sup> Tregs is linked to the formation of the inhibitors in severe HA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this cross\u2010sectional study, 32 patients with severe HA (8 patients with inhibitors and 24 without inhibitors) and 24 healthy controls were enrolled. The frequency of FOXP3<jats:sup>+<\/jats:sup> Tregs was determined using multicolor flow cytometry method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed that the median level of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>FOXP3<jats:sup>+<\/jats:sup> Tregs did not significantly differ between HA patients and healthy controls and between HA patients with and without inhibitors (<jats:italic>P<\/jats:italic>\u2009&gt;\u20090.05). However, patients with inhibitors had significantly lower amounts of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup>FOXP3<jats:sup>+<\/jats:sup> Tregs compared to those without inhibitors as well as healthy controls (*<jats:italic>P<\/jats:italic>\u2009=\u20090.012 and *<jats:italic>P<\/jats:italic>\u2009=\u20090.004, respectively). The frequency of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T cells was significantly higher in HA patients who developed inhibitors compared to the inhibitor\u2010negative ones whereas they were lower in inhibitor\u2010negative patients compared to the healthy controls (*P\u2009=\u20090.013 and *<jats:italic>P<\/jats:italic>\u2009=\u2009*0.029, respectively). The percentages of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T cells were positively correlated with the levels of inhibitors in HA patients (<jats:italic>r<\/jats:italic>\u2009=\u20090.45, *<jats:italic>P<\/jats:italic>\u2009=\u20090.021).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data demonstrated for the first time that the CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup>FOXP3<jats:sup>+<\/jats:sup> Tregs might be implicated in the prevention of inhibitor formation in severe HA patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.14139","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T05:46:03Z","timestamp":1690263963000},"page":"953-960","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Altered frequency of <scp>FOXP3<\/scp><sup>+<\/sup> regulatory T cells is associated with development of inhibitors in patients with severe hemophilia A"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6489-0979","authenticated-orcid":false,"given":"Nargess","family":"Arandi","sequence":"first","affiliation":[{"name":"Hematology Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid Reza","family":"Zekavat","sequence":"additional","affiliation":[{"name":"Hematology Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negin","family":"Shokrgozar","sequence":"additional","affiliation":[{"name":"Hematology Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Shahsavani","sequence":"additional","affiliation":[{"name":"Hematology Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Golmoghaddam","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Kalani","sequence":"additional","affiliation":[{"name":"Department of Immunology, Professor Alborzi Clinical Microbiology Research Center Shiraz University of Medical Sciences  Shiraz 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