Assessment of interleukin-10 promoter variant (−1082A/G) and cytokine production in patients with hemolytic uremic syndrome

Author:

Mongelos Micaela Aldana,Sosa Fernando Nicolás,Pineda Gonzalo Ezequiel,Fiorentino Gabriela,Santiago Adriana,Abelleyro Miguel Martín,Rossetti Liliana Carmen,Exeni Ramón,De Brasi Carlos Daniel,Palermo Marina Sandra,Ramos María Victoria

Abstract

IntroductionHemolytic uremic syndrome (HUS) is a condition that results in acute kidney failure mainly in children, which is caused by Shiga toxin–producing Escherichia coli and inflammatory response. Although anti-inflammatory mechanisms are triggered, studies on the implication in HUS are scarce. Interleukin-10 (IL-10) regulates inflammation in vivo, and the interindividual differences in its expression are related to genetic variants. Notably, the single nucleotide polymorphism (SNP) rs1800896 −1082 (A/G), located in the IL-10 promoter, regulates cytokine expression.MethodsPlasma and peripheral blood mononuclear cells (PBMC) were collected from healthy children and HUS patients exhibiting hemolytic anemia, thrombocytopenia, and kidney damage. Monocytes identified as CD14+ cells were analyzed within PBMC by flow cytometry. IL-10 levels were quantified by ELISA, and SNP −1082 (A/G) was analyzed by allele-specific PCR.ResultsCirculating IL-10 levels were increased in HUS patients, but PBMC from these patients exhibited a lower capacity to secrete this cytokine compared with those from healthy children. Interestingly, there was a negative association between the circulating levels of IL-10 and inflammatory cytokine IL-8. We observed that circulating IL-10 levels were threefold higher in HUS patients with −1082G allele in comparison to AA genotype. Moreover, there was relative enrichment of GG/AG genotypes in HUS patients with severe kidney failure.DiscussionOur results suggest a possible contribution of SNP −1082 (A/G) to the severity of kidney failure in HUS patients that should be further evaluated in a larger cohort.

Publisher

Frontiers Media SA

Subject

Pediatrics, Perinatology and Child Health

Reference50 articles.

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