Role of complement in alloimmunization and hyperhemolysis

• Authors: Satheesh Chonat, Emory University; Amanda Mener, Emory University; Hans Verkerke, Emory University; Sean Stowell, Emory University
• Journal Title: CURRENT OPINION IN HEMATOLOGY
• Volume: Volume 27, Number 6
• Publisher: LIPPINCOTT WILLIAMS & WILKINS | 2020-11-01, Pages 406-414
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/MOH.0000000000000610
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Hematology; alloimmunization; anemia; complement; hyperhemolysis; transfusion; SICKLE-CELL-DISEASE; MEMBRANE ATTACK COMPLEX; RED-BLOOD-CELLS; ANTIGEN MODULATION; TRANSFUSION REACTION; ACTIVATION; ANTIBODY; ERYTHROCYTE; IMMUNOLOGY; PATHWAY

Abstract

PURPOSE OF REVIEW: The purpose of this review is to summarize the role of complement in regulating the removal of a target alloantigen following an incompatible red blood cell (RBC) transfusion, the formation of alloantibodies following RBC alloantigen exposure, and the development of hyperhemolysis in patients with sickle cell disease (SCD). RECENT FINDINGS: Recent studies demonstrate that complement can accelerate alloantibody-mediated removal of target alloantigens from the RBC surface following incompatible transfusion. Complement also influences alloantigen availability during developing alloimmune responses and serves as a unique mediator of CD4 T-cell-independent alloantibody formation following RBC alloantigen exposure. Finally, alternative complement pathway activation appears to play a key role in the development of acute hemolytic episodes in patients with SCD, providing a potential druggable target to prevent acute complications in patients with this disease. SUMMARY: Recent studies suggest that complement can regulate a wide variety of processes germane to hematology, from transfusion complications to baseline hemolysis in patients with SCD. As the role of complement in various disease processes becomes more fully understood, the ability to leverage recently developed complement modulating drugs will only continue to enhance providers' ability to favorably intervene in many hematological diseases.