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J Immunol. 2017 Aug 1;199(3):1041-1050. doi: 10.4049/jimmunol.1700401. Epub 2017 Jun 19.

Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice.

Author information

1
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520.
2
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520.
3
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520.
4
Bloodworks Northwest Research Institute, Seattle, WA 98102.
5
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA 98195.
6
Division of Hematology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195; and.
7
Howard Hughes Medical Institute, Chevy Chase, MD 20815.
8
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520; jeanne.hendrickson@yale.edu.

Abstract

During RBC transfusion, production of alloantibodies against RBC non-ABO Ags can cause hemolytic transfusion reactions and limit availability of compatible blood products, resulting in anemia-associated morbidity and mortality. Multiple studies have established that certain inflammatory disorders and inflammatory stimuli promote alloimmune responses to RBC Ags. However, the molecular mechanisms underlying these findings are poorly understood. Type I IFNs (IFN-α/β) are induced in inflammatory conditions associated with increased alloimmunization. By developing a new transgenic murine model, we demonstrate that signaling through the IFN-α/β receptor is required for inflammation-induced alloimmunization. Additionally, mitochondrial antiviral signaling protein-mediated signaling through cytosolic pattern recognition receptors was required for polyinosinic-polycytidylic acid-induced IFN-α/β production and alloimmunization. We further report that IFN-α, in the absence of an adjuvant, is sufficient to induce RBC alloimmunization. These findings raise the possibility that patients with IFN-α/β-mediated conditions, including autoimmunity and viral infections, may have an increased risk of RBC alloimmunization and may benefit from personalized transfusion protocols and/or targeted therapies.

PMID:
28630094
PMCID:
PMC5568771
DOI:
10.4049/jimmunol.1700401
[Indexed for MEDLINE]
Free PMC Article

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