title: Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and β-thalassemia major.
abstract: 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.
authors.affiliation: Laboratory of Complement Biology, New York Blood Center, 310 E67th Street, 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: Xiaojuan
authors.initials: X
authors.lastname: Li
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Lee
authors.forename: Joseph
authors.initials: J
authors.lastname: Schwartz
authors.forename: Sujit
authors.initials: S
authors.lastname: Sheth
authors.forename: Karina
authors.initials: K
authors.lastname: Yazdanbakhsh
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015331:Cohort Studies; D005260:Female; D006450:Hemoglobin SC Disease / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D006720:Homozygote; D006801:Humans; D056747:Immunomodulation; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D007378:Interleukins / Q000097:blood / Q000378:metabolism; D007518:Isoantibodies / Q000032:analysis; D007519:Isoantigens / Q000009:adverse effects*; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D065227:Transfusion Reaction; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000628:therapy
chemical_list: D015415:Biomarkers; D007378:Interleukins; D007518:Isoantibodies; D007519:Isoantigens; D007371:Interferon-gamma