Expression of immune checkpoint CD28 rs1980422-related single-nucleotide polymorphisms in primary immune thrombocytopenia

Abstract

Background
The pathogenesis of immune thrombocytopenia (ITP) implies a hyperactivated T cell response, which plays a key role in cell-mediated cytotoxicity and IgG production. The aim of this work was to inspect the expression of immune checkpoint CD28 rs1980422-related single-nucleotide polymorphisms in primary ITP, and to compare the expression immune checkpoint CD28 rs1980422-related single-nucleotide polymorphisms in primary ITP in adult patients and in children.


Patients and methods
This case–control study was carried out on 70 patients diagnosed with ITP, both sexes, aged from 1 to 60 years old and 30 healthy volunteers serving as controls age-matched and sex-matched. Patients were included two groups: group I: 30 healthy control participants, and group II: 70 patients diagnosed with ITP. All patients underwent a clinical assessment, laboratory investigations (direct Coombs test, and genotyping).


Results

Univariate logistic regression identified several factors significantly associated with ITP risk, including white blood cells [odds ratio (OR)=1.3,
P
=0.033], red blood cells (OR=0.437,
P
=0.018), hemoglobin (OR=0.67,
P
=0.002), mean corpuscular hemoglobin concentration (OR=0.71,
P
=0.033), and red blood cell distribution width (OR=1.58,
P
=0.009). In the multivariate model, white blood cells (OR=1.49,
P
=0.039) remained significantly associated with ITP risk. The CT genotype of rs1980422 also showed a significant related to ITP risk in both univariate (OR=4.64,
P
=0.006) and multivariate models (OR=5.84,
P
=0.008), indicating its potential role as a genetic marker for ITP susceptibility.



Conclusion
CT genotypes were linked to lower platelet counts and increased bleeding severity, suggesting that the CT genotype may serve as a potential genetic marker for disease severity and prognosis. This highlights the role of genetic variations in T-cell co-stimulatory pathways in the pathogenesis of ITP through altered immune regulation.