Conflict of interest: Nothing to report
Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and β-thalassemia major†
Article first published online: 26 SEP 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Hematology
Volume 86, Issue 12, pages 1001–1006, December 2011
How to Cite
Bao, W., Zhong, H., Li, X., Lee, M. T., Schwartz, J., Sheth, S. and Yazdanbakhsh, K. (2011), Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and β-thalassemia major. Am. J. Hematol., 86: 1001–1006. doi: 10.1002/ajh.22167
- Issue published online: 16 NOV 2011
- Article first published online: 26 SEP 2011
- Accepted manuscript online: 11 AUG 2011 04:04PM EST
- Manuscript Accepted: 8 AUG 2011
- Manuscript Revised: 2 AUG 2011
- Manuscript Received: 18 JUL 2011
- National Heart, Lung, and Blood Institute. Grant Number: R21HL097350
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.