HLA Alloimmunization in Pediatric Sickle Cell Disease andThalassemia Major:Prevalence and Risk factors Open Access

Abstract

Individuals who require blood transfusion are at risk for alloimmunization against foreign human antigens. Alloimmunization to red blood cells (RBC) occurs commonly in sickle cell disease (SCD) and thalassemia major and limits the ability to safely transfuse blood. Alloimmunization to human leukocyte antigens (HLA) can occur with RBC transfusions and may result in severe transfusion reactions and graft rejection in organ and stem cell transplantation. The prevalence and risk factors for HLA alloimmunization are unknown in SCD and thalassemia patients requiring frequent transfusions. A cross-sectional study of HLA alloantibodies in pediatric patients with SCD and thalassemia major was performed to test the hypothesis that HLA alloimmunization occurs at a frequency equal to or greater than RBC alloimmunization. All thalassemia major patients in Atlanta were tested. SCD patients were selected to match for presence or absence of RBC antibodies and chronic transfusion therapy. Over a 3-year period, 17 thalassemia major and 73 SCD patients were sampled. HLA alloimmunization was seen in 53% of SCD patients with RBC antibodies and 21% without RBC antibodies (OR 4.32 [1.55 - 12.1]). In multivariate logistic regression, RBC antibodies were predictive of HLA antibodies and showed interaction with chronic transfusion exposure. In thalassemia patients, the prevalence of HLA alloimmunization was 47%. This analysis is the first description of HLA alloimmunization in SCD patients and in pediatric thalassemia major patients transfused in the U.S. and demonstrates that individual predisposition to alloimmunization is common for both RBC and HLA antigens.

Table of Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 4. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 5. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 6. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 7. Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

About this Dissertation

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School	Laney Graduate School
Department	Clinical Research Curriculum Program
Degree	MS
Submission	Dissertation
Language	English
Research Field	Health Sciences, Medicine and Surgery Health Sciences, Epidemiology
Keyword	HLA thalassemia sickle cell alloimmunization
Committee Chair / Thesis Advisor	Boring, John R, Emory University
Committee Members	Hillyer, Christopher D, Emory University Klein, Mitchel, Emory University

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