BACKGROUND: Alloimmunization to antigens on transfused red blood cells (RBCs) represents a major barrier to chronic transfusion. In extreme cases of multiple alloimmunization, clinicians may be faced with the decision of transfusing incompatible RBCs or risking death from lack of transfusion. The disastrous results of hemolytic transfusion reactions are well understood, and major pathways of clearance have been described. However, well described but poorly understood is the survival of a subset of incompatible donor RBCs during hemolysis, despite antibody binding. STUDY DESIGN AND METHODS: We utilize a tractable murine model of incompatible transfusion in which RBCs from transgenic donor mice expressing human glycophorin A (hGPA) are transfused into recipients passively immunized with anti-hGPA. RESULTS: As in humans, the majority of RBCs are cleared but a subset of incompatible donor RBCs persist in circulation, despite being bound by antibodies. Data contained herein reject the hypothesis that lack of clearance is due to insufficient antibody or overwhelming of phagocytic machinery; rather, we establish that surviving RBCs represent a distinct population resistant to clearance. CONCLUSIONS: These studies demonstrate that surviving RBCs during incompatible transfusion can represent a population that is resistant to clearance.
BACKGROUND: Alloimmunization to antigens on transfused red blood cells (RBCs) represents a major barrier to chronic transfusion. In extreme cases of multiple alloimmunization, clinicians may be faced with the decision of transfusing incompatible RBCs or risking death from lack of transfusion. The disastrous results of hemolytic transfusion reactions are well understood, and major pathways of clearance have been described. However, well described but poorly understood is the survival of a subset of incompatible donor RBCs during hemolysis, despite antibody binding. STUDY DESIGN AND METHODS: We utilize a tractable murine model of incompatible transfusion in which RBCs from transgenic donormice expressing human glycophorin A (hGPA) are transfused into recipients passively immunized with anti-hGPA. RESULTS: As in humans, the majority of RBCs are cleared but a subset of incompatible donor RBCs persist in circulation, despite being bound by antibodies. Data contained herein reject the hypothesis that lack of clearance is due to insufficient antibody or overwhelming of phagocytic machinery; rather, we establish that surviving RBCs represent a distinct population resistant to clearance. CONCLUSIONS: These studies demonstrate that surviving RBCs during incompatible transfusion can represent a population that is resistant to clearance.
Authors: Connie M Arthur; Jerry William L Allen; Hans Verkerke; Justin Yoo; Ryan P Jajosky; Kathryn Girard-Pierce; Satheesh Chonat; Patricia Zerra; Cheryl Maier; Jen Rha; Ross Fasano; Cassandra D Josephson; John D Roback; Sean R Stowell Journal: Blood Adv Date: 2021-01-26
Authors: Sean R Stowell; Kathryn R Girard-Pierce; Nicole H Smith; Kate L Henry; C Maridith Arthur; James C Zimring; Jeanne E Hendrickson Journal: Transfusion Date: 2013-04-29 Impact factor: 3.157
Authors: Sean R Stowell; Kate L Henry; Nicole H Smith; Krystalyn E Hudson; Greg R Halverson; Jaekeun C Park; Ashley M Bennett; Kathryn R Girard-Pierce; C Maridith Arthur; Silvia T Bunting; James C Zimring; Jeanne E Hendrickson Journal: Blood Date: 2013-06-25 Impact factor: 22.113
Authors: Amanda Mener; Seema R Patel; Connie M Arthur; Satheesh Chonat; Andreas Wieland; Manjula Santhanakrishnan; Jingchun Liu; Cheryl L Maier; Ryan P Jajosky; Kathryn Girard-Pierce; Ashley Bennett; Patricia E Zerra; Nicole H Smith; Jeanne E Hendrickson; Sean R Stowell Journal: JCI Insight Date: 2018-11-15
Authors: Connie M Arthur; Satheesh Chonat; Ross Fasano; Marianne E M Yee; Cassandra D Josephson; John D Roback; Sean R Stowell Journal: Transfus Med Rev Date: 2019-10-18
Authors: Marianne E M Yee; Cassandra D Josephson; Anne M Winkler; Jennifer Webb; Naomi L C Luban; Traci Leong; Sean R Stowell; John D Roback; Ross M Fasano Journal: Transfusion Date: 2018-04-17 Impact factor: 3.337