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Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With IL2RA and PTPN2 Gene Polymorphisms

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  • Magdalena Keindl
  • Olena Fedotkina
  • Elsa du Plessis
  • Ruchi Jain
  • Brith Bergum
  • Troels Mygind Jensen
  • Cathrine Laustrup Møller
  • Henrik Falhammar
  • Thomas Nyström
  • Sergiu-Bogdan Catrina
  • Gun Jörneskog
  • Leif Groop
  • Mats Eliasson
  • Björn Eliasson
  • Kerstin Brismar
  • Peter M Nilsson
  • Tore Julsrud Berg
  • Silke Appel
  • Valeriya Lyssenko
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Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic β cells. Further, patients with T1D have 3-4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naïve to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care.

OriginalsprogEngelsk
TidsskriftFrontiers in Endocrinology
Vol/bind11
Sider (fra-til)575469
ISSN1664-2392
DOI
StatusUdgivet - 30 okt. 2020

Bibliografisk note

Copyright © 2020 Keindl, Fedotkina, du Plessis, Jain, Bergum, Mygind Jensen, Laustrup Møller, Falhammar, Nyström, Catrina, Jörneskog, Groop, Eliasson, Eliasson, Brismar, Nilsson, Berg, Appel and Lyssenko.

ID: 61242929