title: Mechanisms of sickle cell alloimmunization.
abstract: Red blood cell (RBC) alloimmunization can be a life-threatening complication for patients with sickle cell disease (SCD) receiving therapeutic transfusions. Despite provision of extended antigen-matched donor RBCs, patients continue to develop antibodies due to high degree of polymorphisms in the immunogenic antigens in individuals of African ancestry. Identification of biomarkers of alloimmunization in this patient population is therefore of great interest and will help to identify in advance patients most likely to make antibodies in response to transfusion. We have recently identified altered T cell responses and innate immune abnormalities in alloimmunized SCD patients. In this paper, we summarize this work and propose our working model of how innate immune abnormalities can contribute to pathogenic T cell responses in alloimmunized SCD patients. We believe that unravelling the basis of such altered interactions at the cellular and molecular level will help future identification of biomarkers of alloimmunization with the goal that this information will ultimately help guide therapy in these patients.
authors.affiliation: Laboratory of Complement Biology, New York Blood Center, 310, East 67th Street, 10065 New York, United States. Electronic address: kyazdanbakhsh@nybloodcenter.org.
authors.forename: K
authors.initials: K
authors.lastname: Yazdanbakhsh
mesh_terms: D000755:Anemia, Sickle Cell / Q000201:enzymology / Q000276:immunology* / Q000628:therapy; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers; D001787:Blood Group Incompatibility / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D004912:Erythrocytes / Q000276:immunology*; D006418:Heme / Q000276:immunology; D051547:Heme Oxygenase-1 / Q000172:deficiency / Q000502:physiology; D006427:Hemin / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D007518:Isoantibodies / Q000096:biosynthesis* / Q000276:immunology; D008211:Lymphocyte Cooperation; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology; D018448:Models, Immunological; D009000:Monocytes / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D065227:Transfusion Reaction
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; D007518:Isoantibodies; D008565:Membrane Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D006418:Heme; D006427:Hemin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Allo-immunisation; Alloimmunization; Drépanocytose; Heme; Heme oxygenase; Hème; Hème oxygénase; Sickle cell; Th1; Transfusion; Transfusions; Tregs