Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms in a cohort of Egyptian patients with immune thrombocytopenia (ITP)

Doaa Mohamed El Demerdash; Maha Mohamed Saber; Alia Ayad; Kareeman Gomaa; Mohamed Abdelkader Morad

doi:10.1007/s44313-024-00011-z

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms in a cohort of Egyptian patients with immune thrombocytopenia (ITP)

Blood Res. 2024 Mar 1;59(1):8. doi: 10.1007/s44313-024-00011-z.

Authors

Doaa Mohamed El Demerdash¹, Maha Mohamed Saber², Alia Ayad², Kareeman Gomaa³, Mohamed Abdelkader Morad²

Affiliations

¹ Internal Medicine Department, Faculty of Medicine, Teaching Kasr AL-Ainy Hospital, Cairo University, Al Kasr Al Aini, Old Cairo, 4240310, Cairo Governorate, Egypt. dr_eldemerdash@kasralainy.edu.eg.
² Internal Medicine Department, Faculty of Medicine, Teaching Kasr AL-Ainy Hospital, Cairo University, Al Kasr Al Aini, Old Cairo, 4240310, Cairo Governorate, Egypt.
³ Clinical and Chemical Pathology Department, Faculty of Medicine, Kasr AL-Ainy Hospital, Cairo University, Cairo, Egypt.

Abstract

Background: Immune thrombocytopenia (ITP) is characterized by immune response dysregulations. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a central role in immune checkpoint pathways and preventing autoimmune diseases by regulating immune tolerance. We aimed to explore the potential association between CTLA-4 gene polymorphisms and ITP as well as study their impact on the response to therapy.

Methods: We investigated two CTLA-4 single-nucleotide polymorphisms (SNPs; rs: 231775 and rs: 3087243) using real-time PCR as well as the plasma levels of CTLA-4 by ELISA in 88 patients with ITP and 44 healthy participants (HC).

Results: CTLA-4 (rs: 3087243) A > G polymorphism analysis showed most HC had the homozygous AA genotype, which was statistically significant compared to patients with ITP. Plasma levels of CTLA4 were statistically lower in patients with acute ITP. There was no correlation between CTLA-4 (rs: 231775 and rs: 3087243) A/G SNPs were not correlated to the response to all lines of therapy assessed (corticosteroids, thrombopoietin receptor agonists, splenectomy, and rituximab).

Conclusion: CTLA-4 CT 60 A/G may affect the susceptibility of ITP, but both CTLA-4 + 49 A/G and CT60 A/G did not impact the response of patients with ITP to different lines of therapy.

Keywords: CTLA-4; ITP; Immune checkpoints; Immune thrombocytopenia; SNPs.