Frontiers in Immunology (Jun 2023)

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

  • Anna-Mari Schroderus,
  • Josh Poorbaugh,
  • Samantha McElyea,
  • Stephanie Beasley,
  • Lin Zhang,
  • Kirsti Näntö-Salonen,
  • Reeta Rintamäki,
  • Jussi Pihlajamäki,
  • Jussi Pihlajamäki,
  • Mikael Knip,
  • Mikael Knip,
  • Mikael Knip,
  • Riitta Veijola,
  • Jorma Toppari,
  • Jorma Toppari,
  • Jorma Ilonen,
  • Robert J. Benschop,
  • Tuure Kinnunen,
  • Tuure Kinnunen

DOI
https://doi.org/10.3389/fimmu.2023.1157265
Journal volume & issue
Vol. 14

Abstract

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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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