Regulatory B Cells Are Functionally Impaired in Patients Having Hemophilia A With Inhibitors

Mohamed Rachid Boulassel, Maryam Al-Ghonimi, Badriya Al-Balushi, Amal Al-Naamani, Zahra Al-Qarni, Yasser Wali, Mohamed Elshinawy, Maryam Al-Shezawi, Hamad Khan, Hanan Nazir, Doaa Khater, Anil Pathare, Salam Al-Kindi

Research output: Contribution to journalArticle

Abstract

Development of inhibitors remains a major clinical complication in patients with hemophilia A receiving replacement therapy with factor VIII (FVIII). Understanding the immune mechanisms involved in the development of inhibitors can provide valuable information about pathways to human tolerance. Recent evidence indicates that B regulatory (Breg) cells play a pivotal role in controlling the production of antibodies (Abs) while promoting follicular T helper (Tfh) cells and monocytes, expressing the low-density lipoprotein receptor-related protein (LRP/CD91), which is involved in FVIII intake from the circulation. We studied circulating levels of Breg cells along with Tfh cells and the expression of LRP/CD91 on monocytes in patients with hemophilia A using 8-color flow cytometry and cell culture. Compared to healthy controls, patients with hemophilia A with inhibitors showed a severe reduction in levels of Breg cells and produced less interleukin-10 when activated via the CD40 signaling pathway. In addition, patients with hemophilia A with inhibitors exhibited an overexpression of LPR/CD91 on monocytes and normal levels of Tfh cells. Levels of Breg cells were not significantly related to LPR/CD91 although negative associations were evidenced. Collectively, these results provide new insights into the role of Breg cells and LPR/CD91 in the development of inhibitors in patients with hemophilia A.

Original languageEnglish
Pages (from-to)618-624
Number of pages7
JournalClinical and Applied Thrombosis/Hemostasis
Volume24
Issue number4
DOIs
Publication statusPublished - May 1 2018

Keywords

  • B regulatory cells
  • follicular cells
  • hemophilia A
  • inhibitors
  • LPR

ASJC Scopus subject areas

  • Hematology

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