Immunological mechanisms associated with long‐term remission of human type 1 diabetes

Karges, Beate; Durinovic‐Belló, Ivana; Heinze, E.; Debatin, Klaus‐Michael; Boehm, Bernhard O.; Karges, Wölfram

doi:10.1002/dmrr.600

Cited by 27 publications

(19 citation statements)

References 24 publications

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“…Hence, it is suggested that these cells may predict good clinical outcomes by a specific regulatory response [39, 40]. Interestingly, a predominant IL-10 cytokine profile (and low IFN-γ secretion) in peripheral blood mononuclear cells was observed in 1 T1D patient with complete remission, with reported β-cell function [41]. Moreover, low serum IFN-γ concentrations at T1D clinical onset provide a strong positive predictive value for partial remission [42].…”

Section: Collateral Damage Of the T1d Remission Phase And Newly Propomentioning

confidence: 99%

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

Fonolleda¹,

Murillo²,

Vázquez

et al. 2017

Horm Res Paediatr

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Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the β-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of β-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children. Shortly after diagnosis, T1D patients often experience partial remission called “honeymoon phase,” which lasts a few months, with minor requirements of exogenous insulin. In this stage, the remaining β-cells are still able to produce enough insulin to reduce the administration of exogenous insulin. A recovery of immunological tolerance to β-cell autoantigens could explain the regeneration attempt in this remission phase. This mini-review focuses on the remission phase in childhood T1D. Understanding this period and finding those peripheral biomarkers that are signs of immunoregulation or islet regeneration could contribute to the identification of patients with a better glycaemic prognosis and a lower risk of secondary complications. This remission phase could be a good checkpoint for the administration of future immunotherapies.

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Section: Collateral Damage Of the T1d Remission Phase And Newly Propomentioning

confidence: 99%

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

Fonolleda¹,

Murillo²,

Vázquez

et al. 2017

Horm Res Paediatr

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“…This difference was not observed between children with diabetes recognized at a later age and age-matched healthy controls. The results of animal (Perez et al 2008;Cheatem et al 2009) as well as human studies (Karges et al 2006) highlight the role of cytokines IL-10 and TGF-b in the pathogenesis of T1D. Karges et al (2006) concluded that IL-10-dependent regulatory CD4 ?…”

Section: Discussionmentioning

confidence: 99%

“…The results of animal (Perez et al 2008;Cheatem et al 2009) as well as human studies (Karges et al 2006) highlight the role of cytokines IL-10 and TGF-b in the pathogenesis of T1D. Karges et al (2006) concluded that IL-10-dependent regulatory CD4 ? T cell pathways are involved in b-cell recovery after the onset of hyperglycemia in autoimmune T1D.…”

Section: Discussionmentioning

confidence: 99%

Low Frequency of Regulatory T Cells in the Peripheral Blood of Children with Type 1 Diabetes Diagnosed under the Age of Five

Szypowska

Stelmaszczyk-Emmel

Demkow

et al. 2012

Arch. Immunol. Ther. Exp.

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The highest annual increase in the incidence of type 1 diabetes (T1D) in children under the age of 5 years and aggressive process of β-cell destruction in this age group indicate the need to assess the immune system. The aim of this study was to evaluate regulatory T cells (Tregs) frequency in the peripheral blood of children <5 years of age with newly diagnosed T1D in comparison with diabetic children diagnosed at a later age and healthy controls. 40 children with newly diagnosed T1D (20 children <5 years of age and 20 older patients) and 40 age-matched controls were included in this study. Flow cytometric analysis of Tregs was performed using the following markers: CD4, CD25, CD127, FoxP3, IL-10, and TGF-β. Apoptosis was measured using anti-active caspase 3 monoclonal antibody. Fasting C-peptide and HbA1c were monitored as well. We showed that T1D children <5 years had lower C-peptide concentration than diabetic children ≥5 years of age (0.32 vs. 0.80 ng/ml, respectively, p = 0.0005). There was lower frequency of CD4(+)CD25(high)CD127(low)FoxP3(+) Tregs in T1D children <5 years than ≥5 years of age (0.87 vs. 1.56 %, respectively, p = 0.017). Diabetic children <5 years had lower CD4(+)CD25(high)CD127(low)FoxP3(+), CD4(+)CD25(high)IL-10, and CD4(+)CD25(high)TGF-β Tregs compared to age-matched controls. There was no difference in Tregs apoptosis between the examined groups. This study highlights the distinctiveness of diabetes in children <5 years of age. Understanding the differences of immune system activity in the young diabetic children would open the way to identify children at risk for T1D and enables the use of novel forms of intervention.

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“…It appears that there may be efficient regeneration of β-cells in children with T1D or having undergone subtotal pancreatectomy 5,67,68 . Also, insulin+/glucagon+ bihormonal cells have been described in human diabetic patients 69–71 and upon ex vivo epigenetic manipulation 72 , suggesting that human α-cells might also display the plasticity allowing insulin production.…”

Section: Prospectivementioning

confidence: 99%

Regeneration of pancreatic insulin-producing cells by in situ adaptive cell conversion

Chera

Herrera

2016

Current Opinion in Genetics & Development

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The impaired ability to produce or respond to insulin, a hormone synthetized by the pancreatic β-cells, leads to diabetes. There is an excruciating need of finding new approaches to protect or restore these cells once they are lost. Replacement and ex vivo directed reprogramming methods have an undeniable therapeutic potential, yet they exhibit crucial flaws. The in vivo conversion of adult cells to functional insulin-producing cells is a promising alternative for regenerative treatments in diabetes. The stunning natural transdifferentiation potential of the adult endocrine pancreas was recently uncovered. Modulating molecular targets involved in β-cell fate maintenance or in general differentiation mechanisms can further potentiate this intrinsic cell plasticity, which leads to insulin production reconstitution.

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Immunological mechanisms associated with long‐term remission of human type 1 diabetes

Abstract: Our observations support the concept that IL-10-dependent regulatory CD4(+) T-cell pathways are involved in beta cell recovery after the onset of hyperglycemia in autoimmune type 1 DM.

Cited by 27 publications

References 24 publications

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

Low Frequency of Regulatory T Cells in the Peripheral Blood of Children with Type 1 Diabetes Diagnosed under the Age of Five

Regeneration of pancreatic insulin-producing cells by in situ adaptive cell conversion

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