PMID- 26636339
OWN - NLM
STAT- MEDLINE
DCOM- 20160626
LR  - 20220311
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 12
DP  - 2015
TI  - Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 
      Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.
PG  - e0142976
LID - 10.1371/journal.pone.0142976 [doi]
LID - e0142976
AB  - 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-1beta (but not IL-6 
      or tumor necrosis factor [TNF]-alpha), 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.
FAU - Alnek, Kristi
AU  - Alnek K
AD  - Department of Immunology, Institute of Bio- and Translational Medicine, 
      University of Tartu, Estonia.
FAU - Kisand, Kalle
AU  - Kisand K
AD  - Department of Immunology, Institute of Bio- and Translational Medicine, 
      University of Tartu, Estonia.
FAU - Heilman, Kaire
AU  - Heilman K
AD  - Tallinn Children's Hospital, Tallinn, Estonia.
AD  - Department of Pediatrics, University of Tartu, Tartu, Estonia.
FAU - Peet, Aleksandr
AU  - Peet A
AD  - Department of Pediatrics, University of Tartu, Tartu, Estonia.
AD  - Children's Clinic of Tartu University Hospital, Tartu, Estonia.
FAU - Varik, Karin
AU  - Varik K
AD  - Surgery Clinic of Tartu University Hospital, Tartu, Estonia.
FAU - Uibo, Raivo
AU  - Uibo R
AD  - Department of Immunology, Institute of Bio- and Translational Medicine, 
      University of Tartu, Estonia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151204
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Autoantibodies)
RN  - 0 (Cytokines)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
SB  - IM
MH  - Adolescent
MH  - Age of Onset
MH  - Autoantibodies/blood
MH  - Child
MH  - Cytokines/*blood
MH  - Diabetes Mellitus, Type 1/*blood/diagnosis
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*blood
MH  - Male
MH  - Th17 Cells/*immunology
MH  - Young Adult
PMC - PMC4670260
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/12/05 06:00
MHDA- 2016/06/28 06:00
PMCR- 2015/12/04
CRDT- 2015/12/05 06:00
PHST- 2015/04/22 00:00 [received]
PHST- 2015/10/29 00:00 [accepted]
PHST- 2015/12/05 06:00 [entrez]
PHST- 2015/12/05 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
PHST- 2015/12/04 00:00 [pmc-release]
AID - PONE-D-15-17097 [pii]
AID - 10.1371/journal.pone.0142976 [doi]
PST - epublish
SO  - PLoS One. 2015 Dec 4;10(12):e0142976. doi: 10.1371/journal.pone.0142976. 
      eCollection 2015.