Association of interferon-γ and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes

Abstract

SummaryWe studied whether serum interferon (IFN)-γ γ γ γ or interleukin (IL)-10 levels and their corresponding functional polymorphic genotypes are associated with partial remission of type 1 diabetes (T1D). A multi-centre study was undertaken in patients with newly diagnosed T1D and matched controls. T1D patients were followed for 3 months and characterized for remission status. Partial clinical remission was defined as a daily insulin dose ≤ ≤ ≤ ≤ 0·38 units/kg/ 24 h with an HbA1c ≤ ≤ ≤ ≤ 7·5%. Thirty-three patients and 32 controls were phenotyped for serum concentrations of IFN-γ γ γ γ and IL-10 and genotyped for functional polymorphisms of the IFN-γ γ γ γ and IL-10 genes. Sixteen of 25 informative patients (63%) remitted. Serum IFN-γ γ γ γ concentrations were significantly decreased in remitters but increased in non-remitters compared to controls, and did not change over time in any group. IFN-γ γ γ γ genotypes corresponded with serum levels in controls and non-remitters, but not in remitters who displayed the lowest serum IFN-γ γ γ γ levels despite more often carrying high-producing IFN-γ γ γ γ genotypes. Neither the frequency of IL-10 genotypes nor serum IL-10 concentration differed between patients and controls. The combination of high-producing IFN-γ γ γ γ genotype together with low serum IFN-γ γ γ γ concentration at the time of diagnosis provided a strong positive predictive value for remission. Serum IFN-γ γ γ γ concentrations predicted by genotype and observed serum levels were discordant in remitters, suggestive of regulation overruling genetic predisposition. Although high-producing genotypes were less frequent in remitters, they were predictive of remission in combination with low serum IFN-γ γ γ γ levels. These data imply that remission is partially immunemediated and involves regulation of IFN-γ γ γ γ transcription.

Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies

“…In a limited cross-sectional prospective study, we found that higher FoxP3 expression at diagnosis predicted worse glycemic control, but higher mean numbers of IL-10 cells were associated with better future glucose control. Additionally, others reported lower IFN-␥ levels in remitters (12). Together, these data suggest that there may be an immunological component underlying the honeymoon phase, arguing for antigen-specific immunomodulation to curb autoimmunity soon after diagnosis.…”

Association between age, IL‐10, IFNγ, stimulated C‐peptide and disease progression in children with newly diagnosed Type 1 diabetes

“…Yet, even although the distribution of the genetic variants was equal among the progression groups, rapidly progressing patients had significantly higher levels of IFNc compared with other progression groups. Conversely, we have previously shown that patients in clinical remission, defined by HbA 1c £ 58 mmol ⁄ -mol (7.5%) and insulin requirement £ 0.38 U kg -1 day -1 , had significantly lower IFNc levels than patients not in remission, in spite of the presence of IFNc genotypes associated with high IFNc production [14]. IFNc has been described as a key molecule in b-cell destruction [7].…”

“…, while there were no associations with either IL-10 levels or genotype frequencies [14]. In this study, we tested the hypothesis that IL-10 and IFNc serum levels in combination with their respective genotypes are associated with disease progression in paediatric patients with newly diagnosed Type 1 diabetes.…”

Drak2 Is Upstream of p70S6 Kinase: Its Implication in Cytokine-Induced Islet Apoptosis, Diabetes, and Islet Transplantation

“…We treated islets with a combination of IFN-␥ and IL-1␤ or TNF-␣ and IL-1␤, which are reported to cause islet apoptosis in type 1 diabetes (14,15). The islets were harvested 2, 6, and 24 h after the cytokine stimulation.…”