Emory University School of Medicine, Georgia, United States
Background/Case Studies: Patients with sickle cell disease (SCD) have high RBC alloimmunization rates. Those prone to form RBC alloantibody after RBC exposure can be typed as ‘responders’ versus ‘non-responders’ that fail to make RBC alloantibody despite hundreds of RBC transfusions. Some individuals form multiple RBC alloantibodies, so called ‘hyper-responders’. We hypothesized that the underlying inflammatory state in SCD thought to play a role in RBC alloantibody formation and responder type may impact antibody response to non-RBC immunogenic stimuli. To explore this, we analyzed IgG antibody level in COVID-19 vaccinated patients with SCD.
Study
Design/Methods: Anti-SARS-CoV-2 receptor-binding domain (RBD)-specific IgG level measured by ELISA in residual clinical serum samples from COVID-19 vaccinated patients with SCD at a single institution. RBC alloantibody and transfusion history obtained by chart review. The latter was categorized as ‘minimal’ if never or rarely transfused, ‘chronic’ if ever on chronic transfusion program, and ‘episodic’ for all others. Autoantibodies were excluded in the RBC alloantibody count. Statistical difference assessed by Kruskal-Wallis (group) and Mann-Whitney (pair) test.
Results/Findings: RBC alloantibody history was available for 158 patients of which 42 had ≥1 RBC alloantibody (26.6%). Patients were grouped by RBC transfusion history and number of RBC alloantibody for the RBD IgG endpoint titer comparison (Table 1). There was no statistical difference among the minimal (p = 0.1610) and episodic (p = 0.8079) transfusion history group. Overall comparison in the chronic transfusion group nearly reached statistical significance (p = 0.0643) and pair comparison of hyper-responders (≥2 alloantibody) with non-responders (0 alloantibody despite heavy RBC exposure) showed a nearly 1-log titer difference that was statistically significant (253839 vs 30951, p = 0.0228). Conclusions: Our study suggests RBC alloimmunization hyper-responders generate higher IgG antibody response to COVID-19 vaccination compared to non-responders in the chronic transfusion group, which may be due to underlying inflammation in patients with SCD. Analysis of additional vaccine immune responses may potentially uncover association with RBC alloimmunization responder type.
Importance of research: RBC alloimmunization can lead to delays in finding compatible RBC for transfusion and puts patients at risk for acute/delayed hemolytic transfusion reactions. Prediction of RBC alloimmunization responder type would allow for prioritization of antigen-matched RBC units to mitigate RBC alloimmunization and its clinical consequences. Our study suggests immune response to vaccination may potentially identify responder type and merits further investigation.
