Frequency of CD40-1C>T polymorphism (rs1883832) and association with response to treatment in children with primary immune thrombocytopenia

Objectives: To investigate whether (cluster of differentiation) CD40-1C>T (rs1883832) contributes to predisposition and treatment response of primary immune thrombocytopenia (pITP) in children.

Methods: A case–control study that included 100 children with newly diagnosed pITP and 50 age- and sex-matched healthy controls. CD40 rs1883832 was genotyped using TaqMan allele discrimination real-time polymerase chain reaction (PCR). Patients were categorized into responders and non-responders according to their response to corticosteroids and thrombopoietin-receptor agonists (TPO-RA) at 3-month intervals.

Results: The genotypic distribution of the CD40 rs1883832 was significantly different among cases and controls (CC 48% vs. 30%; CT 44% vs. 42%; TT 8% vs. 28%; p = .003). Compared with controls, children with newly diagnosed pITP had significantly higher C allele frequency (70% vs. 51%; odds ratio [OR] 2.2, 95% confidence interval [CI]: 1.3–3.8; p = .001). The association between C allele frequency and pITP risk was evident in females (OR 4.3, 95% CI: 2.1–8.8; p < .001), but not in males (OR 0.9, 95% CI: 0.4–2.1; p = .822). Compared with responders, the C allele frequency was significantly higher among non-responders to corticosteroids (87% vs. 66%; OR 3.4, 95% CI: 1.2–11.7; p = .012), but not to TPO-RA (92% vs. 85%; OR 2, 95% CI: 0.2–107; p = .550).

Conclusion: CD40 rs1883832 polymorphism may contribute to predisposition and response to upfront corticosteroids therapy of pediatric pITP. These findings improve our understanding of the compound pathophysiology of ITP, suggest important clinical potentials, and open the door for further research on the mechanistic role of CD40 rs1883832 in ITP development and progression.