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Evaluation of regulatory T cells frequency and FoxP3/GDF-15 gene expression in β-thalassemia major patients with and without alloantibody; correlation with serum ferritin and folate levels

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Abstract

β-thalassemia major is one of the most common hematologic disorders in the world. It causes severe anemia and patients require regular blood transfusions, which causes different complications such as iron overload and alloimmunization. Regulatory T cells (Tregs) have an important role in regulation of immune responses. FoxP3 is the major marker of Tregs and its expression can be influenced by different factors. GDF-15 is another gene that plays a role in iron homeostasis and regulation of immune system in different diseases. The aim of this study was to assess the frequency of Tregs and FoxP3/GDF-15 gene expression in β-thalassemia major patients with and without alloantibody as well as its correlation with different factors such as serum ferritin and folate levels. This study was conducted on 68 β-thalassemia major patients with and without alloantibodies in comparison with 20 healthy individuals with matched age and sex as control group. Enzyme-linked immunosorbent assay (ELISA), flow cytometry, and real-time PCR were performed in order to evaluate serum ferritin and folate levels, frequency of Tregs, and the expression of FoxP3 and GDF-15 genes, respectively. The percentage and absolute count of Tregs were increased in patients compared with controls (P = 0.0003), but there was no difference between responders and non-responders (P > 0.05). The Tregs count correlated positively with serum ferritin. No correlation was observed between target genes and serum ferritin and folate, but there was a positive significant correlation between the expression of FoxP3 and GDF-15 genes, which shows the immunosuppressive role of GDF-15.

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Acknowledgments

The authors would like to thank the staffs of Diagnostic Laboratory Sciences and Technology Research Center. Also, the authors wish to thank Mr. H. Argasi at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript.

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Correspondence to Sedigheh Sharifzadeh.

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The study was approved by the local ethics committee of Shiraz University of Medical Sciences. Written informed consent was obtained from each patient enrolled in the study.

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Shokrgozar, N., Amirian, N., Ranjbaran, R. et al. Evaluation of regulatory T cells frequency and FoxP3/GDF-15 gene expression in β-thalassemia major patients with and without alloantibody; correlation with serum ferritin and folate levels. Ann Hematol 99, 421–429 (2020). https://doi.org/10.1007/s00277-020-03931-9

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  • DOI: https://doi.org/10.1007/s00277-020-03931-9

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