Regulatory T-cell phenotypes in children with sickle cell disease

Asmaa M Zahran; Khaled Saad; Khalid I Elsayh; Shaimaa M Khalaf; Khaled Hashim Mahmoud; Amira Elhoufey; Helal F Hetta

doi:10.1038/s41390-021-01627-y

Regulatory T-cell phenotypes in children with sickle cell disease

Pediatr Res. 2022 Apr;91(5):1203-1206. doi: 10.1038/s41390-021-01627-y. Epub 2021 Jun 18.

Authors

Asmaa M Zahran¹, Khaled Saad², Khalid I Elsayh³, Shaimaa M Khalaf³, Khaled Hashim Mahmoud³, Amira Elhoufey^{4

5}, Helal F Hetta⁶

Affiliations

¹ Department of Clinical pathology, South Egypt Cancer Institute, Assiut, Egypt.
² Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt. khaled.ali@med.au.edu.eg.
³ Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁴ Department of Community Health Nursing, Faculty of Nursing, Assiut University, Assiut, Egypt.
⁵ Department of Community Health Nursing, Alddrab University College, Jazan University, Jazan, Saudi Arabia.
⁶ Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.

PMID: 34145401
DOI: 10.1038/s41390-021-01627-y

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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⁺.

Impact: 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.

MeSH terms

Anemia, Sickle Cell* / drug therapy
Child
Forkhead Transcription Factors
HLA-DR Antigens
Humans
Phenotype
T-Lymphocytes, Regulatory*

Substances

Forkhead Transcription Factors
HLA-DR Antigens