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Regulatory B‐cell compartment in transfused alloimmunized and non‐alloimmunized patients with sickle cell disease
Author(s) -
Bao Weili,
Zhong Hui,
Manwani Deepa,
Vasovic Ljiljana,
Uehlinger Joan,
Lee Margaret T.,
Sheth Sujit,
Shi Patricia,
Yazdanbakhsh Karina
Publication year - 2013
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23488
Subject(s) - immunology , medicine , fetal hemoglobin , biology , pregnancy , fetus , genetics
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 CD24 hi CD38 hi and CD24 hi CD27 + 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. Am. J. Hematol. 88:736–740, 2013. © 2013 Wiley Periodicals, Inc.