A Toll-like receptor 2 genetic variant modulates

Despite adequate immunization and penicillin prophylaxis, bacterial infections remain a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). Besides hyposplenism, inflammatory and genetic factors might modulate their susceptibility to bacterial infections. We performed a candidate gene association of single nucleotide polymorphisms (SNPs) located in Toll-like receptor (TLR) genes, encoding prominent molecules for innate immune responses, with the occurrence of bacterial infections in patients with SCD. A cohort followed in centres in Brazil, France and Senegal (n = 430) was divided in two groups: patients who presented at least one episode of bacterial infection (n = 235) and patients who never had bacterial infections (n = 195). There were no differences in gender or age distribution among the groups. The frequency of the TLR2 rs4696480 TA genotype was significantly lower in the infected group (50% vs. 67%, odds ratio [OR] = 0·50, 95% confidence interval [CI] 0·34–0·75, P < 0·001), and the TT genotype was significantly higher in the infected group (15% vs. 5%, OR = 3·18, 95% CI 1·53–6·61, P < 0·001). Previous reports demonstrated higher secretion of inflammatory factors in cells from AA individuals, lower occurrence and severity of immune diseases in T carriers. The rs4696480 TA genotype might stand between deleterious effects of over inflammatory response (AA genotype) and inefficient responses (TT genotype) to infectious agents in SCD settings.

Keywords

Toll-like receptor, bacterial infections, sickle cell disease, immunization

Citation

Tozatto-Maio et al. (2019) A Toll-like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease. British Journal of Haematology, Volume 185, Issue 5 p. 918-924. https://doi/10.1111/bjh.15875

URI

http://hdl.handle.net/123456789/1443

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STEM

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