HLA alloimmunization is associated with RBC antibodies in multiply transfused patients with sickle cell disease

Alloimmunization to minor red blood cell (RBC) antigens occurs commonly in sickle cell disease (SCD). Patients with alloimmunization demonstrate increased risk for new alloantibody formation with subsequent transfusion. Alloimmunization to human leukocyte antigens (HLA) can occur with RBC transfusion and may result in graft rejection during stem cell or organ transplantation. The prevalence and risk factors for HLA alloimmunization in multiply transfused pediatric SCD patients are unknown.

A cross-sectional study of HLA alloimmunization in SCD patients aged 3-21 years with a history of >or=3 RBC transfusions was performed to test the hypothesis that HLA alloimmunization is associated with RBC alloimmunization. Antibodies to class I and class II HLA were measured by Flow Panel Reactive Antibody (FlowPRA).

Seventy-three SCD patients (30 with RBC antibodies) were tested. HLA antibodies were detected in 25/73 (34%) patients; class I HLA antibodies occurred in 24/73 (33%) and class II HLA antibodies occurred in 3 (4%). Among patients with RBC antibodies, 16/30 (53%) had HLA antibodies, while 9/43 (21%) patients without RBC antibodies had HLA antibodies (OR 4.32 [1.6-12.1]). In a multivariate analysis, antibodies to RBC antigens were an independent predictor of HLA alloimmunization (P = 0.041). The association of RBC and HLA immunization was strongest among patients with no history of chronic transfusion therapy.

This analysis is the first description of HLA alloimmunization in pediatric SCD patients who receive primarily leukoreduced RBC transfusions and demonstrates that HLA alloimmunization tendency is associated with antibodies to RBC antigens.