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.
Front Endocrinol (Lausanne)
; 11: 575469, 2020.
Article
en En
| MEDLINE
| ID: mdl-33193091
ABSTRACT
Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic ß 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo de Nucleótido Simple
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Diabetes Mellitus Tipo 1
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Angiopatías Diabéticas
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Subunidad alfa del Receptor de Interleucina-2
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Proteína Tirosina Fosfatasa no Receptora Tipo 2
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Front Endocrinol (Lausanne)
Año:
2020
Tipo del documento:
Article
País de afiliación:
Noruega