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dc.contributor.authorKeindl, Magdalena
dc.contributor.authorFedotkina, Olena
dc.contributor.authordu Plessis, Elsa
dc.contributor.authorJain, Ruchi
dc.contributor.authorBergum, Brith
dc.contributor.authorMygind Jensen, Troels
dc.contributor.authorLaustrup Møller, Cathrine
dc.contributor.authorFalhammar, Henrik
dc.contributor.authorNyström, Thomas
dc.contributor.authorCatrina, Sergiu-Bogdan
dc.contributor.authorJörneskog, Gun
dc.contributor.authorGroop, Leif
dc.contributor.authorEliasson, Mats
dc.contributor.authorEliasson, Björn
dc.contributor.authorBrismar, Kerstin
dc.contributor.authorNilsson, Peter M.
dc.contributor.authorBerg, Tore Julsrud
dc.contributor.authorAppel, Silke
dc.contributor.authorLyssenko, Valeriya
dc.PublishedFrontiers in Endocrinology. 2020, 11:575469 1-13.
dc.description.abstractType 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.en_US
dc.publisherFrontiers Mediaen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleIncreased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With IL2RA and PTPN2 Gene Polymorphismsen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2020 Keindl, Fedotkina, du Plessis, Jain, Bergum, Mygind Jensen, Laustrup Møller, Falhammar, Nyström, Catrina, Jörneskog, Groop, Eliasson, Eliasson, Brismar, Nilsson, Berg, Appel and Lyssenko.en_US
dc.source.journalFrontiers in Endocrinologyen_US
dc.identifier.citationFrontiers in Endocrinology. 2020, 11, 575469.en_US

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