Alloimmunization against RBC or PLT antigens is independent of TRIM21 expression in a murine model.
Generation of alloantibodies to transfused RBCs can be a serious medical problem for patients who require chronic RBC transfusion therapy. Patients with sickle cell disease have a substantially increased rate of alloimmunization compared to other chronically transfused populations. A recent study has forwarded the hypothesis that a polymorphism in an immunoregulatory gene in close proximity to beta-globin (TRIM21 rs660) plays a role in the increased rates of RBC alloimmunization in sickle cell patients. In particular, it was hypothesized that rs660C/T decreases expression of TRIM21, resulting in loss of a negative feedback pathway in immune responses and increased RBC alloimmunization. To test the effects of TRIM21 expression on alloimmunization, we analyzed antibody responses to alloantigens on RBCs and platelets transfused into wild-type and TRIM21 KO mice. No significant increases were seen in the frequency or magnitude of humoral immunization to alloantigens on transfused RBCs or platelets in adult or juvenile TRIM21 KO recipients compared to wild-type controls. Moreover, recipient inflammation with poly (I:C) enhanced RBC alloimmunization to similar degrees in both TRIM21 KO and wild-type control recipients. Together, these data rule out the hypothesis that decreased TRIM21 expression enhances transfusion induced humoral alloimmunization, in the context of a reductionist murine model.
Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Seema R
SR
Patel
Jeanne E
JE
Hendrickson
Nicole H
NH
Smith
Chantel M
CM
Cadwell
Keiko
K
Ozato
Herbert C
HC
Morse
Ryusuke
R
Yoshimi
James C
JC
Zimring
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology*; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology*; D005260:Female; D056724:Immunity, Humoral / Q000187:drug effects; D007114:Immunization; D007249:Inflammation / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D017713:Platelet Transfusion; D011070:Poly I-C / Q000494:pharmacology; D012261:Ribonucleoproteins / Q000378:metabolism; D000099207:SS-A Antigen
D000941:Antigens; D007518:Isoantibodies; D011070:Poly I-C; D012261:Ribonucleoproteins; D000099207:SS-A Antigen
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