A Toll-like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease

Karina Tozatto-Maio, Robert Girot, Indou D Ly, Vanderson Rocha, Ana C Silva Pinto, Ibrahima Diagne, Yahia Benzerara, Carla L Dinardo, Simone Kashima, Itauá Leston-Araujo, Chantal Kenzey, Guilherme H H Fonseca, Evandra S Rodrigues, Fernanda Volt, Luciana R Jarduli, Annalisa Ruggeri, Christina M Mariaselvam, Sandra F M Gualandro, Hanadi Elayoubi, Renato CunhaBarbara Cappelli, Kelen C R Malmegrim, Belinda P Simões, Eliane Gluckman, Ryad Tamouza

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Abstract

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.

Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusE-pub ahead of print - Mar 25 2019

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Tozatto-Maio, K., Girot, R., Ly, I. D., Rocha, V., Silva Pinto, A. C., Diagne, I., Benzerara, Y., Dinardo, C. L., Kashima, S., Leston-Araujo, I., Kenzey, C., Fonseca, G. H. H., Rodrigues, E. S., Volt, F., Jarduli, L. R., Ruggeri, A., Mariaselvam, C. M., Gualandro, S. F. M., Elayoubi, H., ... Tamouza, R. (2019). A Toll-like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease. British Journal of Haematology. https://doi.org/10.1111/bjh.15875