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Immune regulation in chronically transfused allo‐antibody responder and nonresponder patients with sickle cell disease and β‐thalassemia major
Author(s) -
Bao Weili,
Zhong Hui,
Li Xiaojuan,
Lee Margaret T.,
Schwartz Joseph,
Sheth Sujit,
Yazdanbakhsh Karina
Publication year - 2011
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.22167
Subject(s) - immunology , medicine , antibody , immune system , thalassemia , disease , isoantibodies
Red blood cell alloimmunization is a major complication of transfusion therapy. Host immune markers that can predict antibody responders remain poorly described. As regulatory T cells (Tregs) play a role in alloimmunization in mouse models, we analyzed the Treg compartment of a cohort of chronically transfused patients with sickle cell disease (SCD, n = 22) and β‐thalassemia major ( n = 8) with and without alloantibodies. We found reduced Treg activity in alloantibody responders compared with nonresponders as seen in mice. Higher circulating anti‐inflammatory IL‐10 levels and lower IFN‐γ levels were detected in non‐alloimmunized SCD patients. Stimulated sorted CD4+ cells from half of the alloimmunized patients had increased frequency of IL‐4 expression compared with nonresponders, indicating a skewed T helper (Th) 2 humoral immune response in a subgroup of antibody responders. All patients had increased Th17 responses, suggesting an underlying inflammatory state. Although small, our study indicates an altered immunoregulatory state in alloantibody responders which may help future identification of potential molecular risk factors for alloimmunization. Am. J. Hematol. 2011. © 2011 Wiley‐Liss, Inc.