Increased Interleukin-35 Levels in Patients With Type 1 Diabetes With Remaining C-Peptide
| Autor: | Stellan Sandler, Daniel Espes, Kailash Singh, Per-Ola Carlsson |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male 0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism CD8-Positive T-Lymphocytes T-Lymphocytes Regulatory 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin-Secreting Cells Internal medicine Diabetes mellitus Internal Medicine medicine Humans Insulin In patient Advanced and Specialized Nursing Type 1 diabetes C-Peptide C-peptide business.industry Interleukins Interleukin-17 Cell Differentiation Middle Aged medicine.disease Diabetes Mellitus Type 1 030104 developmental biology Endocrinology chemistry Case-Control Studies Interleukin 35 Leukocytes Mononuclear Th17 Cells Female business 030215 immunology |
| Zdroj: | Diabetes Care. 40:1090-1095 |
| ISSN: | 1935-5548 0149-5992 |
| Popis: | OBJECTIVE Many patients with long-standing type 1 diabetes have remaining functional β-cells. This study investigated immunological differences between patients with or without measurable remaining endogenous insulin production after ≥10 years duration of disease. RESEARCH DESIGN AND METHODS Patients (n = 113; ≥18 years of age) with type 1 diabetes and with disease duration of ≥10 years were recruited at Uppsala University Hospital. Residual β-cell function was determined with an ultrasensitive C-peptide ELISA. Circulating cytokines, including interleukin-35 (IL-35), were determined in plasma. Additional blood samples were collected from 14 of the identified C-peptide–positive patients and 12 of the C-peptide–negative patients, as well as from 15 healthy control subjects, and were used for immediate investigation of peripheral blood mononuclear cells. RESULTS The blood concentration of the cytokine IL-35 was markedly lower in C-peptide–negative patients, and this was associated with a simultaneous decrease in the proportion of IL-35+ regulatory T cells (Tregs), IL-35+ regulatory B cells, and IL-35–producing CD8+Foxp3+ cells. IL-35 has previously been shown to maintain the phenotype of Tregs, block the differentiation of T-helper 17 cells, and thereby dampen immune assaults to β-cells. We found that the proportions of IL-17a+ cells among the Tregs, CD4+ T cells, and CD8+ T cells were lower in the C-peptide–positive patients. CONCLUSIONS Patients with remaining endogenous β-cell function after >10 years duration of type 1 diabetes differ immunologically from other patients with long-standing type 1 diabetes. In particular, they have a much higher IL-35 production. |
| Databáze: | OpenAIRE |
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