Antigen density dictates RBC clearance, but not antigen modulation, following incompatible RBC transfusion in mice

• Type of Material: Article
• Authors: Connie Arthur, Emory University; Jerry William L. Allen, Emory University; Hans Verkerke, Emory University; Justin Yoo, Emory University; Ryan P. Jajosky, Emory University; Kathryn Girard-Pierce, Emory University; Satheesh Chonat, Emory University; Patricia Zerra, Emory University; Cheryl Maier, Emory University; Jen Rha, Emory University; Ross Fasano, Emory University; Cassandra Josephson, Emory University; John Roback, Emory University; Sean Stowell, Emory University
• Language: English
• Date: 2021-01-23
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by The American Society of Hematology
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2020002695
• Title of Journal or Parent Work: Blood Advances
• Volume: 5
• Issue: 2
• Start Page: 527
• End Page: 538
• Grant/Funding Information: This work was supported in part by National Institutes of Health, National Heart, Lung, and Blood Institute grants R01 HL138656 and P01 HL132819 (S.R.S.) and R01 HL135575 (S.R.S. and J.D.R.)
• Keywords: Hyperhaemolysis syndrome; Hematology; Alloantibodies; Complement; FC-gamma receptors; Life Sciences & Biomedicine; Antibody; Science & Technology; Red blood cell; Sickle cell disease; Adult patients; Mouse models; Alloimmunization
• Research Categories: Health Sciences, Rehabilitation and Therapy; Health Sciences, Oncology; Biology, Cell; Health Sciences, Immunology

Abstract

Incompatible red blood cell (RBC) transfusion can result in life-threatening transfusion complications that can be challenging to manage in patients with transfusion-dependent anemia. However, not all incompatible RBC transfusions result in significant RBC removal. One factor that may regulate the outcome of incompatible RBC transfusion is the density of the incompatible antigen. Despite the potential influence of target antigen levels during incompatible RBC transfusion, a model system capable of defining the role of antigen density in this process has not been developed. In this study, we describe a novel model system of incompatible transfusion using donor mice that express different levels of the KEL antigen and recipients with varying anti-KEL antibody concentrations. Transfusion of KEL1 RBCs that express high or moderate KEL antigen levels results in rapid antibody-mediated RBC clearance. In contrast, relatively little RBC clearance was observed following the transfusion of KEL RBCs that express low KEL antigen levels. Intriguingly, unlike RBC clearance, loss of the KEL antigen from the transfused RBCs occurred at a similar rate regardless of the KEL antigen density following an incompatible transfusion. In addition to antigen density, anti-KEL antibody levels also regulated RBC removal and KEL antigen loss, suggesting that antigen density and antibody levels dictate incompatible RBC transfusion outcomes. These results demonstrate that antibody-induced antigen loss and RBC clearance can occur at distinct antigen density thresholds, providing important insight into factors that may dictate the outcome of an incompatible RBC transfusion.