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

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.