High T‐helper‐1 cytokines but low T‐helper‐3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes

Stechova, Katerina; Böhmová, Kristýna; Vrabelová, Zuzana; Sepa, Annelie; Stadlerova, Gabriela; Zacharovová, K.; Faresjö, Maria

doi:10.1002/dmrr.718

Cited by 46 publications

(44 citation statements)

References 51 publications

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“…In line with this hypotheses, it was observed that children still able to secrete C-peptide at diagnosis showed an immune response including proinflammatory (TNF-α), Th2-like (IL-13), and, to some extent, also Tr1-like (IL-10) immune markers. This immune response may mirror a still ongoing autoimmune attack of the remaining β cells and confirms our previous observation of an inflammatory immune response at the onset of disease (20,21). Moreover, a higher stimulated cytokine secretion seen in T1D, despite low spontaneous secretion, could speculatively be due to the generation of memory cells recognizing the putative autoantigens and thereby augment the immune response upon restimulation in vitro.…”

Section: Discussionsupporting

confidence: 87%

General immune dampening is associated with disturbed metabolism at diagnosis of type 1 diabetes

et al. 2013

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Section: Discussionsupporting

confidence: 87%

General immune dampening is associated with disturbed metabolism at diagnosis of type 1 diabetes

et al. 2013

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“…We observed that exclusively the Th1-associated cytokine IFN-g was elevated in high-stressed children. This is of interest, because we, as well as others, have shown a Th1-like dominance by high IFN-g secretion in children with high risk for development of T1D (33,(43)(44)(45). Previous studies have shown that IFN-g inhibits proliferation of Th2 and Th17 (46,47), which correlates well with our results of low levels of Th2 and Th17 versus high levels of Th1.…”

Section: Discussionsupporting

confidence: 91%

“…PBMCs were then incubated at 37˚C, in a humified atmosphere with 5% CO 2 with medium exclusively (spontaneous secretion), or stimulated with Ag or autoantigen (Table II). All seven Ags have been explored in previous studies (32,33), and order of priority in case of inadequate cell count was spontaneous, glutamic acid decarboxylase 65 (GAD 65 ) protein, heat shock protein 60 (HSP60) peptide, tetanus toxoid (TT), tyrosine phosphatase (IA-2) peptide, GAD 65 peptide, insulin peptide, b-lactoglobulin (bLG), and finally, PHA. PBMCs were harvested after 72 h of stimulation.…”

Section: In Vitro Culturing Of Pbmcsmentioning

confidence: 99%

Psychological Stress in Children May Alter the Immune Response

Carlsson

Frostell

Ludvigsson

et al. 2014

The Journal of Immunology

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Psychological stress is a public health issue even in children and has been associated with a number of immunological diseases. The aim of this study was to examine the relationship between psychological stress and immune response in healthy children, with special focus on autoimmunity. In this study, psychological stress was based on a composite measure of stress in the family across the domains: 1) serious life events, 2) parenting stress, 3) lack of social support, and 4) parental worries. PBMCs, collected from 5-y-old high-stressed children (n = 26) and from 5-y-old children without high stress within the family (n = 52), from the All Babies In Southeast Sweden cohort, were stimulated with Ags (tetanus toxoid and β-lactoglobulin) and diabetes-related autoantigens (glutamic acid decarboxylase 65, insulin, heat shock protein 60, and tyrosine phosphatase). Immune markers (cytokines and chemokines), clinical parameters (C-peptide, proinsulin, glucose), and cortisol, as an indicator of stress, were analyzed. Children from families with high psychological stress showed a low spontaneous immune activity (IL-5, IL-10, IL-13, IL-17, CCL2, CCL3, and CXCL10; p < 0.01) but an increased immune response to tetanus toxoid, β-lactoglobulin, and the autoantigens glutamic acid decarboxylase 65, heat shock protein 60, and tyrosine phosphatase (IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, CCL2, CCL3, and CXCL10; p < 0.05). Children within the high-stress group showed high level of cortisol, but low level of C-peptide, compared with the control group (p < 0.05). This supports the hypothesis that psychological stress may contribute to an imbalance in the immune response but also to a pathological effect on the insulin-producing β cells.

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“…This is in agreement with a previously documented 39 We have also previously reported that PMBCs from young patients with T1D, predominantly produced Th3 cytokines IL-10 and TGF-b. 40,41 However, a predominant secretion of TGF-b over IL-10 seen in our diabetic quadruplets has not been reported so far. Strikingly, this production pattern exhibited a reverse relation in their pre-diabetic sister.…”

Section: Discussionmentioning

confidence: 63%

Case report: type 1 diabetes in monozygotic quadruplets

et al. 2011

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Type 1 diabetes (T1D) is an autoimmune disease characterized by the lack of insulin due to an autoimmune destruction of pancreatic beta cells. Here, we report a unique case of a family with naturally conceived quadruplets in which T1D was diagnosed in two quadruplets simultaneously. At the same time, the third quadruplet was diagnosed with the pre-diabetic stage. Remarkably, all four quadruplets were positive for anti-islet cell antibodies, GAD65 and IA-A2. Monozygotic status of the quadruplets was confirmed by testing 14 different short tandem repeat polymorphisms. Serological examination confirmed that all quadruplets and their father suffered from a recent enteroviral infection of EV68-71 serotype. To assess the nature of the molecular pathological processes contributing to the development of diabetes, immunocompetent cells isolated from all family members were characterized by gene expression arrays, immune-cell enumerations and cytokine-production assays. The microarray data provided evidence that viral infection, and IL-27 and IL-9 cytokine signalling contributed to the onset of T1D in two of the quadruplets. The propensity of stimulated immunocompetent cells from non-diabetic members of the family to secrete high level of IFN-a further corroborates this conclusion. The number of T regulatory cells as well as plasmacytoid and/or myeloid dendritic cells was found diminished in all family members. Thus, this unique family is a prime example for the support of the so-called 'fertile-field' hypothesis proposing that genetic predisposition to anti-islet autoimmunity is 'fertilized' and precipitated by a viral infection leading to a fully blown T1D.

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High T‐helper‐1 cytokines but low T‐helper‐3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes

Cited by 46 publications

References 51 publications

General immune dampening is associated with disturbed metabolism at diagnosis of type 1 diabetes

General immune dampening is associated with disturbed metabolism at diagnosis of type 1 diabetes

Psychological Stress in Children May Alter the Immune Response

Case report: type 1 diabetes in monozygotic quadruplets

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