title: Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.
abstract: The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.
authors.affiliation: Department of Immunology, Institute of Bio- and Translational Medicine, University of Tartu, Estonia.
authors.forename: Kristi
authors.initials: K
authors.lastname: Alnek
authors.affiliation: Department of Immunology, Institute of Bio- and Translational Medicine, University of Tartu, Estonia.
authors.forename: Kalle
authors.initials: K
authors.lastname: Kisand
authors.affiliation: Tallinn Children's Hospital, Tallinn, Estonia.|Department of Pediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Kaire
authors.initials: K
authors.lastname: Heilman
authors.affiliation: Department of Pediatrics, University of Tartu, Tartu, Estonia.|Children's Clinic of Tartu University Hospital, Tartu, Estonia.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Peet
authors.affiliation: Surgery Clinic of Tartu University Hospital, Tartu, Estonia.
authors.forename: Karin
authors.initials: K
authors.lastname: Varik
authors.affiliation: Department of Immunology, Institute of Bio- and Translational Medicine, University of Tartu, Estonia.
authors.forename: Raivo
authors.initials: R
authors.lastname: Uibo
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D002648:Child; D016207:Cytokines / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D058504:Th17 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins