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
Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (CONICET)-Academia Nacional de Medicina, Buenos Aires, Argentina.
Departamento de Nefrología, Diálisis y Trasplante, Hospital del Niño Prof. Dr. Ramón Exeni, San Justo, Argentina.
Front Pediatr. 2023 Jun 23;11:1210158. doi: 10.3389/fped.2023.1210158. eCollection 2023.
Hemolytic uremic syndrome (HUS) is a condition that results in acute kidney failure mainly in children, which is caused by Shiga toxin-producing and inflammatory response. Although anti-inflammatory mechanisms are triggered, studies on the implication in HUS are scarce. Interleukin-10 (IL-10) regulates inflammation , 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.
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.
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.
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.
溶血尿毒综合征（HUS）是一种主要导致儿童急性肾衰竭的病症，由产志贺毒素和炎症反应引起。尽管会触发抗炎机制，但关于其在HUS中的作用的研究却很少。白细胞介素-10（IL-10）调节炎症，其表达的个体差异与基因变异有关。值得注意的是，位于IL-10启动子中的单核苷酸多态性（SNP）rs1800896 -1082（A/G）调节细胞因子的表达。
从健康儿童以及表现出溶血性贫血、血小板减少和肾损伤的HUS患者中采集血浆和外周血单核细胞（PBMC）。通过流式细胞术在PBMC中分析鉴定为CD14细胞的单核细胞。通过酶联免疫吸附测定（ELISA）对IL-10水平进行定量，并通过等位基因特异性PCR分析SNP -1082（A/G）。
HUS患者循环中的IL-10水平升高，但与健康儿童相比，这些患者的PBMC分泌这种细胞因子的能力较低。有趣的是，IL-10的循环水平与炎性细胞因子IL-8之间存在负相关。我们观察到，与AA基因型相比，具有-1082G等位基因的HUS患者循环中的IL-10水平高三倍。此外，在患有严重肾衰竭的HUS患者中，GG/AG基因型相对富集。
我们的结果表明，SNP -1082（A/G）可能对HUS患者肾衰竭的严重程度有影响，这一点应在更大的队列中进一步评估。
