Differential activity of helper T-cell subsets and cytokine signature profiles in alloimmunisation of sickle cell disease.

Abstract

Background and objectives Red blood cell (RBC) transfusion, a cornerstone of therapy in sickle cell disease (SCD), carries the risk of alloimmunisation. Interestingly, not all SCD patients develop alloimmunisation. Research findings underscore the pivotal role of T-cell subsets and their cytokine profiles in regulating alloimmunisation. But the mechanisms of selective alloimmunisation are poorly understood. This study aimed to characterise helper T cell subsets with their signature cytokines in multi-transfused SCD patients. Methods The patients were divided into two groups: alloimmunised and non-alloimmunised, depending on the presence or absence of alloantibodies following transfusions. Flow cytometric analysis of the Tfh and Treg subsets was performed. The supernatant plasma was used to estimate the levels of signature cytokines. The Mann-Whitney U test, independent sample median test, and Spearman's Rho correlation test were performed for statistical analysis. Results A total of 12 patients from each group were included. A significantly higher percentage of T-regs was observed in the non-alloimmunised group [median 7.65, interquartile range (IQR) 6.37-8.20] than in the alloimmunised group (median 6.27, IQR 4.77-6.80) (P<0.05). A significantly higher expression of IL-21 was observed in the alloimmunised group. Significantly higher expression of TGF-β and IL-10 was found in the non-alloimmunised group (P<0.05). Interpretation and conclusions Our study highlights increased Treg percentages and anti-inflammatory cytokine concentrations in the non-immune group, as well as increased pro-inflammatory cytokines and activated Tfh subsets in alloimmunised patients.