Regulatory B-cell compartment in transfused alloimmunized and non-alloimmunized patients with sickle cell disease

Weili Bao, Hui Zhong, Deepa Manwani, Ljiljana Vasovic, Joan Uehlinger, Margaret T. Lee, Sujit Sheth, Patricia Shi, Karina Yazdanbakhsh

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Transfusion therapy is a life-sustaining treatment for patients with sickle cell disease (SCD), but can cause serious complications including alloimmunization. We previously reported diminished regulatory T cells (Tregs) and skewed Th2 responses in alloimmunized SCD patients. We hypothesized that the B cell regulatory (Breg) compartment, which controls Treg and Th differentiation, may also be compromised in allosensitized SCD patients. Phenotypically, we did not find differences in the frequency or numbers of CD24hiCD38hi and CD24hiCD27+ B cell subsets, both previously identified as human Bregs, between alloimmunized and non-alloimmunized SCD patients on regular transfusions. However, at the functional level, CD19+ B cells from alloimmunized SCD patients expressed lower levels of IL-10 following stimulation as compared with non-alloimmunized patients (P < 0.05), and had reduced ability in inhibiting autologous CD14+ monocyte TNF-α expression (P < 0.05). These findings suggest that Bregs from alloimmunized and non-alloimmunized SCD patients differ in their ability to produce IL-10 and dampen monocyte activation, all consistent with an altered immunoregulatory state in alloimmunized SCD patients.

Original languageEnglish (US)
Pages (from-to)736-740
Number of pages5
JournalAmerican Journal of Hematology
Volume88
Issue number9
DOIs
StatePublished - Sep 2013

ASJC Scopus subject areas

  • Hematology

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