Regulatory B Cells Are Functionally Impaired in Patients Having Hemophilia A With Inhibitors.
Clin Appl Thromb Hemost
; 24(4): 618-624, 2018 May.
Article
en En
| MEDLINE
| ID: mdl-28393618
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inmunofenotipificación
/
Linfocitos B Reguladores
/
Hemofilia A
Límite:
Adolescent
/
Child
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Child, preschool
/
Female
/
Humans
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Infant
/
Male
Idioma:
En
Revista:
Clin Appl Thromb Hemost
Asunto de la revista:
ANGIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Omán