HLA Alloimmunization in Pediatric Sickle Cell Disease and Thalassemia Major:Prevalence and Risk factors 公开

McPherson, Marianne Elaine (2009)

Permanent URL: https://etd.library.emory.edu/concern/etds/dz010q71s?locale=zh
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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

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