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Expression of the immune checkpoint receptors CTLA-4, LAG-3, and TIM-3 in β-thalassemia major patients: correlation with alloantibody production and regulatory T cells (Tregs) phenotype

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Abstract

Alloimmunization is a serious complication in β-thalassemia major patients as a result of repeated blood transfusion. The immune checkpoint receptors play an important role in regulating immune system homeostasis and the function of the immune cells. This study aimed to evaluate the expression of cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) immune checkpoint molecules in β-thalassemia major patients with and without alloantibody. For this purpose, 68 β-thalassemia major patients with (34 patients) and without (34 patients) alloantibody as well as 20 healthy controls were enrolled. The expression of these genes was evaluated in different groups of patients by SYBR Green real-time PCR method. Our results showed that the mean expression of LAG-3 was significantly increased in thalassemia patients compared to the control group (*P < 0.001). However, there was no significant difference in expression of the CTLA-4 and TIM-3 as well as LAG-3 genes between patients with and without alloantibody (P > 0.05). A positive correlation was observed between the level of LAG-3 expression with markers associated with Treg function including FOXP3 and GDF-15 genes in β-thalassemia major patients. Taken together, the LAG-3 molecule might have a more prominent role in the abnormality of the immune system in thalassemia patients especially the function of regulatory T cells (Tregs), prior to the CTLA-4 and TIM-3 genes.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was financially supported by a grant provided by Shiraz University of Medical Sciences (grant number 18902).

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Authors and Affiliations

  1. Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Negin Shokrgozar, Mehran Karimi, Narges Rezaei, Vida Moayed & Nargess Arandi

  2. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Hossein Golmoghaddam

  3. Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

    Sedigheh Sharifzadeh

Authors
  1. Negin Shokrgozar
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  2. Mehran Karimi
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  3. Hossein Golmoghaddam
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  4. Narges Rezaei
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  5. Vida Moayed
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  6. Sedigheh Sharifzadeh
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  7. Nargess Arandi
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Contributions

Negin Shokrgozar contributed to performing the research and writing the paper; Mehran Karimi, Hossein Golmoghaddam, and Sedigheh Sharifzadeh contributed to the performing the research and critically revision of the manuscript; and Nargess Arandi contributed to study design, analysis, interpretation of data, writing paper, and performing the research.

Corresponding author

Correspondence to Nargess Arandi.

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Ethics approval

This study was performed according to the ethical standards of the local Ethics Committee of Shiraz University of Medical Sciences (ethical code IR.SUMS.REC.1398.1387) and in compliance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Shokrgozar, N., Karimi, M., Golmoghaddam, H. et al. Expression of the immune checkpoint receptors CTLA-4, LAG-3, and TIM-3 in β-thalassemia major patients: correlation with alloantibody production and regulatory T cells (Tregs) phenotype. Ann Hematol 100, 2463–2469 (2021). https://doi.org/10.1007/s00277-021-04605-w

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