Frequency of toll-like receptor 4 variants and association with treatment response in children with primary immune thrombocytopenia

Heba A Ahmed; Eman M Fahmy; Elsayed Abdelkreem; Ekram A Mahmoud; Asmaa Nafady; Eman H Ahmed

doi:10.1002/pbc.30646

Frequency of toll-like receptor 4 variants and association with treatment response in children with primary immune thrombocytopenia

Pediatr Blood Cancer. 2023 Nov;70(11):e30646. doi: 10.1002/pbc.30646. Epub 2023 Aug 28.

Authors

Heba A Ahmed¹, Eman M Fahmy², Elsayed Abdelkreem², Ekram A Mahmoud³, Asmaa Nafady⁴, Eman H Ahmed⁵

Affiliations

¹ Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt.
² Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt.
³ Department of Microbiology & Immunology, Faculty of Medicine, Sohag University, Sohag, Egypt.
⁴ Department of Clinical and Chemical Pathology, Faculty of Medicine, South Valley University, Qena, Egypt.
⁵ Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

PMID: 37638833
DOI: 10.1002/pbc.30646

Abstract

Objectives: To investigate the frequency of toll-like receptor 4 (TLR4) variants c.896A>G (p.Asp299Gly) and c.1196C>T (p.Thr399Ile) among Egyptian children with primary immune thrombocytopenia (pITP), and their association with disease course and response to treatment.

Methods: A case-control study that included 80 children with pITP and 50 age- and sex-matched healthy controls. TLR4 c.896A>G and c.1196C>T variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Patients were classified according to their response to treatment after 3 months as responders and nonresponders.

Results: Compared with controls, children with pITP had significantly higher minor allele frequencies of TLR4 p.Asp299Gly (16.25% vs. 6%, odds ratio [OR] 3.04, 95% confidence interval [CI]: 1.16-9.36, p = .014) and p.Thr399Ile (20% vs. 4%, OR 6, 95% CI: 2.02-24.01, p < .001). The presence of p.Asp299Gly variant was significantly associated with chronic ITP (OR 7.78, 95% CI: 2.04-35.69, p < .001) and non-response to therapy with steroid (OR 11.67, 95% CI: 1.32-104.08, p = .012), but not thrombopoietin-receptor agonist (OR 1.67, 95% CI: 0.35-8.19, p = .464). Likewise, having p.Thr399Ile variant was significantly associated with chronic ITP (OR 5.14, 95% CI: 1.6-17.4, p = .002) and non-response to therapy with steroid (OR 6.1, 95% CI: 1.01-49.06, p = .046) but not thrombopoietin-receptor agonist (OR 1.57, 95% CI: 0.33-7.58, p = .515).

Conclusion: The presence of TLR4 p.Asp299Gly or p.Thr399Ile variant may be associated with ITP predisposition, chronicity, and non-response to upfront steroid therapy. These findings enhance our understanding of the complex pathophysiology of pITP with potentially important clinical implications.

Keywords: immune thrombocytopenia; predictive genetic testing; prognosis; single nucleotide polymorphism; toll-like receptor 4.

MeSH terms

Case-Control Studies
Child
Disease Progression
Genotype
Humans
Purpura, Thrombocytopenic, Idiopathic* / drug therapy
Purpura, Thrombocytopenic, Idiopathic* / genetics
Toll-Like Receptor 4* / genetics

Substances

Toll-Like Receptor 4