Immune regulation of sickle cell alloimmunization

Red blood cell (RBC) transfusion remains an important treatment for patients with sickle cell disease (SCD), and the majority of patients receive transfusions by adulthood. However, patients with SCD are at a high risk of alloimmunization, which can cause life‐threatening complications. The high rate of alloimmunization can in part be explained by chronic inflammatory condition in SCD characterized by significant immune and inflammatory activation. Heightened immune effector cell responses and/or impaired regulatory networks are likely to drive alloantibody production in alloimmunized SCD patients. In support of this, altered T‐cell immunoregulation, known to control antibody responses, has been reported in alloimmunized SCD patients. In addition, stronger follicular helper T‐cell responses that help antibody production by B cells were described in alloimmunized as compared to non‐alloimmunized SCD patients. Furthermore, several innate immune abnormalities have been identified in alloimmunized SCD patients, including a compromised anti‐inflammatory response against extracellular cell‐free haeme. The data support a model in which alloimmunized SCD patients are unable to switch off their proinflammatory state in response to the ongoing haemolytic state characteristic of SCD, placing this patient subset at a higher risk to develop a strong immune response against allogeneic determinants on transfused RBCs, thus increasing the risk of further alloimmunization. A detai...
Source: ISBT Science Series - Category: Hematology Authors: Tags: Congress Review Source Type: research