Both authors contributed equally to this work.
Transfusion of murine red blood cells expressing the human KEL glycoprotein induces clinically significant alloantibodies
Article first published online: 29 APR 2013
© 2013 American Association of Blood Banks
Volume 54, Issue 1, pages 179–189, January 2014
How to Cite
Stowell, S. R., Girard-Pierce, K. R., Smith, N. H., Henry, K. L., Arthur, C. M., Zimring, J. C. and Hendrickson, J. E. (2014), Transfusion of murine red blood cells expressing the human KEL glycoprotein induces clinically significant alloantibodies. Transfusion, 54: 179–189. doi: 10.1111/trf.12217
This work was supported in part by funding from the National Institutes of Health to JEH (K08 HL092959, R21 HL115696) and to JCZ (P01 HL086773).
- Issue published online: 9 JAN 2014
- Article first published online: 29 APR 2013
- Manuscript Accepted: 14 MAR 2013
- Manuscript Revised: 13 MAR 2013
- Manuscript Received: 6 FEB 2013
- National Institutes of Health. Grant Numbers: K08 HL092959, R21 HL115696, P01 HL086773
Red blood cell (RBC) alloantibodies to nonself antigens may develop after transfusion or pregnancy, leading to morbidity and mortality in the form of hemolytic transfusion reactions or hemolytic disease of the newborn. A better understanding of the mechanisms of RBC alloantibody induction, or strategies to mitigate the consequences of such antibodies, may ultimately improve transfusion safety. However, such studies are inherently difficult in humans.
Study Design and Methods
We recently generated transgenic mice with RBC-specific expression of the human KEL glycoprotein, specifically the KEL2 or KEL1 antigens. Herein, we investigate recipient alloimmune responses to transfused RBCs in this system.
Transfusion of RBCs from KEL2 donors into wild-type recipients (lacking the human KEL protein but expressing the murine KEL ortholog) resulted in dose-dependent anti-KEL glycoprotein immunoglobulin (Ig)M and IgG antibody responses, enhanced by recipient inflammation with poly(I:C). Boostable responses were evident upon repeat transfusion, with morbid-appearing alloimmunized recipients experiencing rapid clearance of transfused KEL2 but not control RBCs. Although KEL1 RBCs were also immunogenic after transfusion into wild-type recipients, transfusion of KEL1 RBCs into KEL2 recipients or vice versa failed to lead to detectable anti-KEL1 or anti-KEL2 responses.
This murine model, with reproducible and clinically significant KEL glycoprotein alloantibody responses, provides a platform for future mechanistic studies of RBC alloantibody induction and consequences. Long-term translational goals of these studies include improving transfusion safety for at-risk patients.