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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Keindl , M , Fedotkina , O , du Plessis , E , Jain , R , Bergum , B , Mygind Jensen , T , Laustrup Moller , C , Falhammar , H , Nystrom , T , Catrina , S-B , Jorneskog , G , Groop , L , Eliasson , M , Eliasson , B , Brismar , K , Nilsson , P M , Berg , T J , Appel , S & Lyssenko , V 2020 , ' 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 ' , Frontiers in Endocrinology , vol. 11 , 575469 . https://doi.org/10.3389/fendo.2020.575469

Title: 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
Author: Keindl, Magdalena; Fedotkina, Olena; du Plessis, Elsa; Jain, Ruchi; Bergum, Brith; Mygind Jensen, Troels; Laustrup Moller, Cathrine; Falhammar, Henrik; Nystrom, Thomas; Catrina, Sergiu-Bogdan; Jorneskog, Gun; Groop, Leif; Eliasson, Mats; Eliasson, Bjorn; Brismar, Kerstin; Nilsson, Peter M.; Berg, Tore Julsrud; Appel, Silke; Lyssenko, Valeriya
Contributor: University of Helsinki, Centre of Excellence in Complex Disease Genetics
Date: 2020-10-30
Language: eng
Number of pages: 13
Belongs to series: Frontiers in Endocrinology
ISSN: 1664-2392
URI: http://hdl.handle.net/10138/322335
Abstract: Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic beta 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 naive 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.
Subject: cardiovascular disease
Cluster of Differentiation 25 (CD25)
diabetes complications
nephropathy
regulatory T cells
retinopathy
sIL-2R
REGULATORY T-CELLS
DISEASE
RETINOPATHY
INDIVIDUALS
AUTOIMMUNE
RISK
SUPPRESSION
MECHANISMS
CYTOKINES
MELLITUS
1184 Genetics, developmental biology, physiology
3121 Internal medicine
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