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

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

Frontiers in Pediatrics

Frontiers Media

Año: 2023

2296-2360

Introduction: Hemolytic 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.Methods: Plasma 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.Results: Circulating 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.Discussion: Our 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.