Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Eli Lilly and Company, Indianapolis, IN, United States.
Front Immunol. 2023 Jun 21;14:1157265. doi: 10.3389/fimmu.2023.1157265. eCollection 2023.
IL-21 is a multifunctional cytokine linked with the pathophysiology of several autoimmune diseases, including type 1 diabetes. In this study, our aim was to examine plasma IL-21 levels in individuals at different stages of type 1 diabetes progression. We measured plasma IL-21 levels, as well as levels of other key pro-inflammatory cytokines (IL-17A, TNF-α and IL-6), from 37 adults with established type 1 diabetes and 46 healthy age-matched adult controls, as well as from 53 children with newly diagnosed type 1 diabetes, 48 at-risk children positive for type 1 diabetes-associated autoantibodies and 123 healthy age-matched pediatric controls using the ultrasensitive Quanterix SiMoA technology. Adults with established type 1 diabetes had higher plasma IL-21 levels compared to healthy controls. However, the plasma IL-21 levels showed no statistically significant correlation with clinical variables, such as BMI, C-peptide, HbA1c, or hsCRP levels, evaluated in parallel. In children, plasma IL-21 levels were almost ten times higher than in adults. However, no significant differences in plasma IL-21 levels were detected between healthy children, autoantibody-positive at-risk children, and children with newly diagnosed type 1 diabetes. In conclusion, plasma IL-21 levels in adults with established type 1 diabetes were increased, which may be associated with autoimmunity. The physiologically high plasma IL-21 levels in children may, however, reduce the potential of IL-21 as a biomarker for autoimmunity in pediatric subjects.
白细胞介素 21（IL-21）是一种多功能细胞因子，与包括 1 型糖尿病在内的几种自身免疫性疾病的病理生理学有关。在这项研究中，我们的目的是检查处于 1 型糖尿病进展不同阶段的个体的血浆 IL-21 水平。我们使用超灵敏的 Quanterix SiMoA 技术，从 37 名确诊的 1 型糖尿病成人和 46 名年龄匹配的健康成人对照者、53 名新诊断的 1 型糖尿病儿童、48 名糖尿病自身抗体阳性的高危儿童和 123 名健康的年龄匹配的儿科对照者中，测量了血浆 IL-21 水平以及其他关键促炎细胞因子（IL-17A、TNF-α 和 IL-6）的水平。与健康对照者相比，确诊的 1 型糖尿病成人的血浆 IL-21 水平更高。然而，并行评估的体重指数（BMI）、C 肽、糖化血红蛋白（HbA1c）或高敏 C 反应蛋白（hsCRP）等临床变量与血浆 IL-21 水平之间无统计学显著相关性。在儿童中，血浆 IL-21 水平几乎是成人的十倍。然而，在健康儿童、糖尿病自身抗体阳性的高危儿童和新诊断的 1 型糖尿病儿童之间，血浆 IL-21 水平没有显著差异。总之，确诊的 1 型糖尿病成人的血浆 IL-21 水平升高，这可能与自身免疫有关。然而，儿童生理性的高血浆 IL-21 水平可能会降低 IL-21 作为儿科自身免疫标志物的潜力。
