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

Autor: Micaela Aldana Mongelos, Fernando Nicolás Sosa, Gonzalo Ezequiel Pineda, Gabriela Fiorentino, Adriana Santiago, Miguel Martín Abelleyro, Liliana Carmen Rossetti, Ramón Exeni, Carlos Daniel De Brasi, Marina Sandra Palermo, María Victoria Ramos
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Pediatrics, Vol 11 (2023)
Druh dokumentu: article
ISSN: 2296-2360
DOI: 10.3389/fped.2023.1210158
Popis: 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.
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