TY - JOUR
T1 - A Toll-like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease
AU - Tozatto-Maio, Karina
AU - Girot, Robert
AU - Ly, Indou D
AU - Rocha, Vanderson
AU - Silva Pinto, Ana C
AU - Diagne, Ibrahima
AU - Benzerara, Yahia
AU - Dinardo, Carla L
AU - Kashima, Simone
AU - Leston-Araujo, Itauá
AU - Kenzey, Chantal
AU - Fonseca, Guilherme H H
AU - Rodrigues, Evandra S
AU - Volt, Fernanda
AU - Jarduli, Luciana R
AU - Ruggeri, Annalisa
AU - Mariaselvam, Christina M
AU - Gualandro, Sandra F M
AU - Elayoubi, Hanadi
AU - Cunha, Renato
AU - Cappelli, Barbara
AU - Malmegrim, Kelen C R
AU - Simões, Belinda P
AU - Gluckman, Eliane
AU - Tamouza, Ryad
N1 - © 2019 British Society for Haematology and John Wiley & Sons Ltd.
PY - 2019/3/25
Y1 - 2019/3/25
N2 - 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.
AB - 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.
U2 - 10.1111/bjh.15875
DO - 10.1111/bjh.15875
M3 - Article
C2 - 30908604
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
ER -