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

Fingerprint

Regulatory B-Lymphocytes
Hemophilia A
Monocytes
Factor VIII
LDL-Receptor Related Proteins
LDL Receptors
Helper-Inducer T-Lymphocytes
Interleukin-10
Antibody Formation
Flow Cytometry
Color
Cell Culture Techniques

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Regulatory B Cells Are Functionally Impaired in Patients Having Hemophilia A With Inhibitors. / Boulassel, Mohamed Rachid; Al-Ghonimi, Maryam; Al-Balushi, Badriya; Al-Naamani, Amal; Al-Qarni, Zahra; Wali, Yasser; Elshinawy, Mohamed; Al-Shezawi, Maryam; Khan, Hamad; Nazir, Hanan; Khater, Doaa; Pathare, Anil; Al-Kindi, Salam.

In: Clinical and Applied Thrombosis/Hemostasis, Vol. 24, No. 4, 01.05.2018, p. 618-624.

Research output: Contribution to journalArticle

Boulassel, Mohamed Rachid ; Al-Ghonimi, Maryam ; Al-Balushi, Badriya ; Al-Naamani, Amal ; Al-Qarni, Zahra ; Wali, Yasser ; Elshinawy, Mohamed ; Al-Shezawi, Maryam ; Khan, Hamad ; Nazir, Hanan ; Khater, Doaa ; Pathare, Anil ; Al-Kindi, Salam. / Regulatory B Cells Are Functionally Impaired in Patients Having Hemophilia A With Inhibitors. In: Clinical and Applied Thrombosis/Hemostasis. 2018 ; Vol. 24, No. 4. pp. 618-624.
@article{c6630494bf1e41e185c19df316deff7a,
title = "Regulatory B Cells Are Functionally Impaired in Patients Having Hemophilia A With Inhibitors",
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.",
keywords = "B regulatory cells, follicular cells, hemophilia A, inhibitors, LPR",
author = "Boulassel, {Mohamed Rachid} and Maryam Al-Ghonimi and Badriya Al-Balushi and Amal Al-Naamani and Zahra Al-Qarni and Yasser Wali and Mohamed Elshinawy and Maryam Al-Shezawi and Hamad Khan and Hanan Nazir and Doaa Khater and Anil Pathare and Salam Al-Kindi",
year = "2018",
month = "5",
day = "1",
doi = "10.1177/1076029617702244",
language = "English",
volume = "24",
pages = "618--624",
journal = "Clinical and Applied Thrombosis/Hemostasis",
issn = "1076-0296",
publisher = "SAGE Publications Inc.",
number = "4",

}

TY - JOUR

T1 - Regulatory B Cells Are Functionally Impaired in Patients Having Hemophilia A With Inhibitors

AU - Boulassel, Mohamed Rachid

AU - Al-Ghonimi, Maryam

AU - Al-Balushi, Badriya

AU - Al-Naamani, Amal

AU - Al-Qarni, Zahra

AU - Wali, Yasser

AU - Elshinawy, Mohamed

AU - Al-Shezawi, Maryam

AU - Khan, Hamad

AU - Nazir, Hanan

AU - Khater, Doaa

AU - Pathare, Anil

AU - Al-Kindi, Salam

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

KW - B regulatory cells

KW - follicular cells

KW - hemophilia A

KW - inhibitors

KW - LPR

UR - http://www.scopus.com/inward/record.url?scp=85042140955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042140955&partnerID=8YFLogxK

U2 - 10.1177/1076029617702244

DO - 10.1177/1076029617702244

M3 - Article

AN - SCOPUS:85042140955

VL - 24

SP - 618

EP - 624

JO - Clinical and Applied Thrombosis/Hemostasis

JF - Clinical and Applied Thrombosis/Hemostasis

SN - 1076-0296

IS - 4

ER -