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Regulatory T-cell phenotypes in children with sickle cell disease



Regulatory T cells (Tregs) are linked to a reduction in alloreactive immune responses, but few studies have investigated the impact of hydroxyurea (HU) therapy on Tregs in sickle cell disease (SCD).


Our case-controlled study presented here included two groups, the first comprising 60 pediatric SCD patients, 30 of whom did not receive any treatment and 30 who received HU, and the second group consisting of 30 healthy controls. Flow cytometry was used to evaluate the percentage of CD4+CD25+highFoxp3+ Tregs present and their phenotypes.


The percentage of CD4+CD25+high Tregs was significantly increased in untreated SCD patients in comparison to treated SCD patients and controls. Conversely, treated SCD children had a lower percentage of CD4+CD25+high Tregs than controls. In addition, a significant increase in the percentage of CD4+CD25+highFoxp3+ Tregs was found in untreated SCD patients, compared to in HU-treated patients and controls. The percentage of naive CD45RA+ Tregs was significantly decreased in untreated SCD patients when compared to other groups.


Among children with SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs by decreasing their frequency, and increasing the proportion of naive CD45RA+ Tregs and reducing levels of the most suppressive Tregs: HLA-DR+, CD39+, and CD69+.


  • Among children with, SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs.

  • HU treatment in SCD decreases the frequency of Tregs, as well as the levels of the most suppressive Tregs: HLA-DR+, CD39+, and CD69+. At the same time, HU increases the proportion of naive CD45RA+ Tregs.

  • Our study showed the impact of HU therapy on Tregs in children with SCD.

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Fig. 1: Flow cytometric detection of regulatory T cells phenotype.


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South Egypt Cancer Institute, Assiut, Egypt (No. 120-2017).

Author information




A.M.Z., K.S., S.K., and A.E. designed the study, followed the patients, analyzed the data, and drafted the manuscript. A.Z. and H.F.H. performed all laboratory investigations in the study. K.I.E, K.S., and K.H.M. drafted the manuscript. All authors were involved in the critical analysis of the final version of the manuscript. All authors approved the manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Khaled Saad.

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The authors declare no competing interests.

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All caregivers of all participants have given their informed written consent.

Ethical approval

All protocols and investigations of our study followed the regulations of the research ethics committee of Assiut University (No. 120-2017).

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Zahran, A.M., Saad, K., Elsayh, K.I. et al. Regulatory T-cell phenotypes in children with sickle cell disease. Pediatr Res (2021).

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