title: Regulatory B-cell compartment in transfused alloimmunized and non-alloimmunized patients with sickle cell disease.
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 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.
authors.affiliation: Laboratory of Complement Biology, New York Blood Center, New York, NY 10065, USA.
authors.forename: Weili
authors.initials: W
authors.lastname: Bao
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.forename: Deepa
authors.initials: D
authors.lastname: Manwani
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Vasovic
authors.forename: Joan
authors.initials: J
authors.lastname: Uehlinger
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Lee
authors.forename: Sujit
authors.initials: S
authors.lastname: Sheth
authors.forename: Patricia
authors.initials: P
authors.lastname: Shi
authors.forename: Karina
authors.initials: K
authors.lastname: Yazdanbakhsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D001803:Blood Transfusion; D005260:Female; D015870:Gene Expression; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000235:genetics / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; C508609:IL10 protein, human; D007126:Immunoglobulin Allotypes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10