Mechanisms of Alloimmunization and Subsequent Bone Marrow Transplantation Rejection Induced by Platelet Transfusion in a Murine Model

Overview

Journal Am J Transplant

Publisher Elsevier

Specialty General Surgery

Date 2012 Feb 4

PMID 22300526

Citations 8

Authors

S R Patel

N H Smith

L Kapp

J C Zimring

Affiliations

Soon will be listed here.

Abstract

For many nonmalignant hematological disorders, HLA-matched bone marrow transplantation (BMT) is curative. However, due to lack of neoplasia, the toxicity of stringent conditioning regimens is difficult to justify, and reduced intensity conditioning is used. Unfortunately, current reduced intensity regimens have high rates of BMT rejection. We have recently reported in a murine model that mHAs on transfused platelet products induce subsequent BMT rejection. Most nonmalignant hematological disorders require transfusion support prior to BMT and the rate of BMT rejection in humans correlates with the number of transfusions given. Herein, we perform a mechanistic analysis of platelet transfusion-induced BMT rejection and report that unlike exposure to alloantigens during transplantation, platelet transfusion primes alloimmunity but does not stimulate full effector function. Subsequent BMT is itself an additional and distinct immunizing event, which does not induce rejection without antecedent priming from transfusion. Both CD4(+) and CD8(+) T cells are required for priming during platelet transfusion, but only CD8(+) T cells are required for BMT rejection. In neither case are antibodies required for rejection to occur.

Citing Articles

Pathophysiology of Alloimmunization.

Molina-Aguilar R, Gomez-Ruiz S, Vela-Ojeda J, Montiel-Cervantes L, Reyes-Maldonado E Transfus Med Hemother. 2020; 47(2):152-159.

PMID: 32355475 PMC: 7184833. DOI: 10.1159/000501861.

Marginal Zone B Cells Induce Alloantibody Formation Following RBC Transfusion.

Patel S, Gibb D, Girard-Pierce K, Zhou X, Rodrigues L, Arthur C Front Immunol. 2018; 9:2516.

PMID: 30505302 PMC: 6250814. DOI: 10.3389/fimmu.2018.02516.

Complement serves as a switch between CD4+ T cell-independent and -dependent RBC antibody responses.

Mener A, Patel S, Arthur C, Chonat S, Wieland A, Santhanakrishnan M JCI Insight. 2018; 3(22).

PMID: 30429364 PMC: 6302935. DOI: 10.1172/jci.insight.121631.

Recipient priming to one RBC alloantigen directly enhances subsequent alloimmunization in mice.

Patel S, Bennett A, Girard-Pierce K, Maier C, Chonat S, Arthur C Blood Adv. 2018; 2(2):105-115.

PMID: 29365318 PMC: 5787868. DOI: 10.1182/bloodadvances.2017010124.

Red blood cell transfusions are associated with HLA class I but not H-Y alloantibodies in children with sickle cell disease.

Nickel R, Hendrickson J, Yee M, Bray R, Gebel H, Kean L Br J Haematol. 2015; 170(2):247-56.

PMID: 25891976 PMC: 4490004. DOI: 10.1111/bjh.13424.

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