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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