Durmus Sinem, Gelisgen Remise, Hajiyeva Ramila, Adrovic Amra, Yildiz Mehmet, Yucesan Emrah, Barut Kenan, Kasapcopur Ozgur, Uzun Hafize
Medical Biochemistry, İzmir Katip Çelebi University Faculty of Medicine, Izmir, Türkiye.
Medical Biochemistry, Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine, Istanbul, Türkiye
BMJ Paediatr Open. 2025 Jan 8;9(1):e003064. doi: 10.1136/bmjpo-2024-003064.
The limited predictive effect of genotype on familial Mediterranean fever (FMF) phenotype suggests that epigenetic factors and alternative mechanisms that may cause IL-1β release could contribute to phenotypic heterogeneity. The objective of this study was to examine the role of IL-1β levels and miR-21-5p, cathepsin B and pyrin levels, which were identified as potential factors causing IL-1β release through the use of bioinformatics tools, in the pathogenesis of FMF and their relationship with disease severity.
50 paediatric patients with FMF and 40 healthy children were enrolled in this study. Patients were divided into subgroups according to Pras disease severity score. Serum miR-21-5p expression levels were assessed by qRT-PCR, while serum pyrin, IL-1β and cathepsin B levels were determined by ELISA.
Serum miR-21-5p was significantly downregulated in FMF patients compared with the control group (p<0.001), while serum pyrin, IL-1β and cathepsin B levels were markedly elevated (p<0.001 for each). Only miR-21-5p was negatively correlated with IL-1β (r=-0.855; p<0.001). In moderately severe FMF patients, miR-21-5p exhibited a statistically significant downregulation (p<0.001), whereas IL-1β and cathepsin B showed a statistically significant increase (p<0.001 and p<0.05, respectively). Furthermore, the Pras score showed a strong negative correlation (r=-0.738; p<0.001) with miR-21-5p levels. Multivariate logistic regression showed that in FMF, a one-unit decrease in miR-21 increased disease severity risk 6.76-fold, while a one-unit increase in cathepsin B raised it 1.71-fold.
This might be considered one of the mechanisms for subclinical inflammation in paediatric FMF patients through increased activation of cytokines via the downregulation of miR-21-5p. Our findings suggest that miR-21-5p and IL-1β play key roles in subclinical inflammation, and these molecules might be a potential therapeutic target.
基因型对家族性地中海热（FMF）表型的预测作用有限，这表明表观遗传因素以及可能导致白细胞介素-1β（IL-1β）释放的其他机制可能导致表型异质性。本研究的目的是探讨IL-1β水平、miR-21-5p、组织蛋白酶B和吡啉水平在FMF发病机制中的作用及其与疾病严重程度的关系，这些因素是通过生物信息学工具确定的可能导致IL-1β释放的潜在因素。
本研究纳入了50例FMF儿科患者和40例健康儿童。根据普拉什疾病严重程度评分将患者分为亚组。通过qRT-PCR评估血清miR-21-5p表达水平，同时通过ELISA测定血清吡啉、IL-1β和组织蛋白酶B水平。
与对照组相比，FMF患者血清miR-21-5p显著下调（p<0.001），而血清吡啉、IL-1β和组织蛋白酶B水平显著升高（各p<0.001）。只有miR-21-5p与IL-1β呈负相关（r=-0.855；p<0.001）。在中度严重FMF患者中，miR-21-5p表现出统计学上的显著下调（p<0.001），而IL-1β和组织蛋白酶B表现出统计学上显著增加（分别为p<0.001和p<0.05）。此外，普拉什评分与miR-21-5p水平呈强负相关（r=-0.738；p<0.001）。多因素逻辑回归显示，在FMF中，miR-21每降低一个单位，疾病严重程度风险增加6.76倍，而组织蛋白酶B每增加一个单位，疾病严重程度风险增加1.71倍。
这可能被认为是儿科FMF患者亚临床炎症的机制之一，即通过miR-21-5p的下调增加细胞因子的激活。我们的研究结果表明，miR-21-5p和IL-1β在亚临床炎症中起关键作用，这些分子可能是潜在的治疗靶点。
