Understanding of the roles of CD4+ CD25+ T cells and tregs in development of anti-FVIII in hemophilia a: Insights for inhibitor development prevention

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dc.authorid0000-0002-5596-9746
dc.authorid0000-0002-8078-2780
dc.authorid0000-0002-0721-6213
dc.authorid0000-0002-2577-9263
dc.authorid0000-0002-7586-6939
dc.contributor.authorAkkaya, Emre
dc.contributor.authorKoç, Başak S.
dc.contributor.authorKüçüksezer, Umut C.
dc.contributor.authorKökoğlu, Ayşenur
dc.contributor.authorÇetin Aktaş, Esin
dc.contributor.authorDeniz, Günnur
dc.contributor.authorGenç, Nilgün Sema
dc.contributor.authorZülfikar, Bülent
dc.date.accessioned2025-11-06T12:13:27Z
dc.date.available2025-11-06T12:13:27Z
dc.date.issued2025
dc.departmentFakülteler, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyokimya Ana Bilim Dalı
dc.description.abstractHemophilia A, characterized by factor VIII (FVIII) deficiency, can be managed with factor replacement therapy. However, FVIII-neutralizing antibodies developed in people with hemophilia A (PwH) can reduce treatment efficacy. This study investigated the impact of FVIII inhibitors on immunity in PwH. Twenty PwH (with the presence and absence of inhibitors) and 10 healthy individuals have participated. CD4+, CD4+CD25+, Treg cell percentages, proliferation levels, and cytokine levels in cell-culture supernatants were evaluated. An increased CD4+CD25+ T-cell subset was noted in PwH without inhibitors. CD4+ and CD4+CD25+ T cells showed increased proliferation, while Treg cells had decreased proliferation in PwH without inhibitors compared to controls. With rFVIII added to cell culture, CD4+CD25+ proliferation decreased and Treg proliferation increased in PwH with inhibitors, while it remained unchanged in other groups. IL-10 was reduced in both PwH groups. TGF-b was decreased in PwH with inhibitors compared to those without inhibitors. IL-10/TGF-b ratio was reduced in both PwH groups compared to controls. rFVIII in culture conditions significantly reduced TNF-a only in PwH with inhibitors, while TGF-b was decreased in PwH without inhibitors and healthy controls. Monitoring T-cell immunity in PwH before anti-FVIII antibody development may improve treatment success and help prevent antibodies and related complications.
dc.identifier.citationAkkaya, E., Koç, B. S., Küçüksezer, U. C., Kökoğlu, A., Çetin Aktaş, E., Deniz, G., Genç, N. S., & Zülfikar, B. (2025). Understanding of the roles of CD4+ CD25+ T cells and tregs in development of anti-FVIII in hemophilia a: Insights for inhibitor development prevention. Blood Coagulation & Fibrinolysis, 36(7), pp. 1-10. https://doi.org/10.1097/MBC.0000000000001393
dc.identifier.doi10.1097/MBC.0000000000001393
dc.identifier.endpage10
dc.identifier.issn0957-5235
dc.identifier.issn1473-5733
dc.identifier.issue7
dc.identifier.scopusqualityQ3
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.1097/MBC.0000000000001393
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1165
dc.identifier.volume36
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorGenç, Nilgün Sema
dc.institutionauthorid0000-0002-2577-9263
dc.language.isoen
dc.publisherLippincott Williams and Wilkins Ltd.
dc.relation.ispartofBlood Coagulation & Fibrinolysis
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectCD4+ CD25+ T Cells
dc.subjectCytokines
dc.subjectFVIII INH
dc.subjectHemophilia A
dc.subjectRFVIII
dc.subjectTreg Cells
dc.titleUnderstanding of the roles of CD4+ CD25+ T cells and tregs in development of anti-FVIII in hemophilia a: Insights for inhibitor development prevention
dc.typeArticle
dspace.entity.typePublication

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