University of Oulu

Schroderus A-M, Poorbaugh J, McElyea S, Beasley S, Zhang L, Näntö-Salonen K, Rintamäki R, Pihlajamäki J, Knip M, Veijola R, Toppari J, Ilonen J, Benschop RJ and Kinnunen T (2023) Evaluation of plasma IL-21 as a potential biomarker for type 1 diabetes progression. Front. Immunol. 14:1157265. doi: 10.3389/fimmu.2023.1157265

Evaluation of plasma IL-21 as a potential biomarker for type 1 diabetes progression

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Author: Schroderus, Anna-Mari1; Poorbaugh, Josh2; McElyea, Samantha2;
Organizations: 1Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
2Eli Lilly and Company, Indianapolis, IN, United States
3Department of Pediatrics, Turku University Hospital, Turku, Finland
4Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland
5Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
6Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
7Pediatric Research Center, New Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
8Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
9PEDEGO Research Unit, Department of Pediatrics, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
10Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, Centre for Population Health Research, University of Turku, Turku, Finland
11Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
12ISLAB Laboratory Centre, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.7 MB)
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Language: English
Published: Frontiers Media, 2023
Publish Date: 2023-09-29


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.

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Series: Frontiers in immunology
ISSN: 1664-3224
ISSN-E: 1664-3224
ISSN-L: 1664-3224
Volume: 14
Article number: 1157265
DOI: 10.3389/fimmu.2023.1157265
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by the Academy of Finland (decision no. 331282) and the Sigrid Jusélius Foundation.
Copyright information: © 2023 Schroderus, Poorbaugh, McElyea, Beasley, Zhang, Näntö-Salonen, Rintamäki, Pihlajamäki, Knip, Veijola, Toppari, Ilonen, Benschop and Kinnunen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.