The aim of this study was to investigate the frequency of a CA dinucleotide repeat polymorphism in the interferon-gamma (IFN-gamma) gene (IFNG) and a C(-590)T polymorphism of the interleukin-4 (IL-4) gene in 236 Caucasoid patients with type 1 diabetes.
Two-thirds of 46 GWAS candidate genes examined were expressed in human islets, and 11 of these significantly changed expression levels following exposure to proinflammatory cytokines (IL-1β + IFNγ + TNFα) for 48 h. Using the GWAS single nucleotide polymorphisms (SNPs) from each locus, we constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D.
Our data revealed that IFN-γ +874T allele carriers [odds ratio (OR) = 1.87, p < 0.001] and TT homozygotes (OR = 1.28, p < 0.001) were significantly more susceptible to developing T1D than the A allele carriers.
Several polymorphisms in regions where Th1 cytokines (IL12B and IFNG genes) are located were analyzed in 303 Spanish subjects with type 1 diabetes and compared with a control cohort (n = 548).
In conclusion, intrinsic mitochondrial dysfunction observed in type 1 diabetes alters mitochondrial ATP and IFNγ production; the latter is correlated with ROS generation.
In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1).
Analysis of an interferon-gamma gene (IFNG) polymorphism in Danish and Finnish insulin-dependent diabetes mellitus (IDDM) patients and control subjects. Danish Study Group of Diabetes in Childhood.
Interleukin (IL)-18 is a potent pro-inflammatory cytokine capable of inducing interferon-gamma production that is associated with the development of T1DM.
IL-18 and IFN-γ have also been implicated in the onset of different types of immune-mediate inflammatory conditions such as Type 1 Diabetes (T1D), Celiac disease (CD), rheumatoid arthritis (RA), obesity and systemic lupus erythematosus (SLE).
IGRP(265-273)-specific CD8 T-cells that were cloned from the peripheral blood of a recent onset T1D individual were shown to secrete IFNγ and Granzyme B after antigen-specific activation and lyse HLA-A2-expressing murine islets in-vitro.
Pro-inflammatory cytokines, such as interleukin-1β and interferon-γ, secreted by the immune cells invading islets of Langerhans, contribute to pancreatic β-cell death in T1D.
The role of endogenous interferon-gamma (IFN gamma) in the development of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone BB rats was evaluated.
We studied helper T-lymphocyte reactivity against β-cell autoantigens by measuring production of the pro-inflammatory cytokine interferon-γ and the anti-inflammatory cytokine interleukin-10, using enzyme-linked immunospot assays in 61 people with Type 1 diabetes (within 3 months of diagnosis, positive for HLA DRB1*0301 and/or *0401), of whom 33 were children/adolescents, and a further 91 were unaffected siblings.
The increased IFN-gamma response and lower IL-4 response toward diabetes-related autoantigens shown in CTLA-4 +49 GG risk subjects show a possible mechanism for the association between CTLA-4 and T1D.
A high proportion of new-onset T1D subjects mounted an inflammatory IFN-γ response much more frequently to one of the mimotope peptides than to the natural peptide.
T cells secreting the cytokines IFN-γ and IL-10 in response to seven peptides known to elicit T cell responses in type 1 diabetes were quantified by cytokine ELISPOT in HLA-typed patients characterized for Abs to IA-2 epitopes.
Through functional analysis of the encoding genes coexpressed by the three lncRNAs, we found these genes were mainly enriched in type 1 diabetes and autoimmune thyroid disease pathways, whereas in Gene Ontology (GO) function classification, they were also mainly enriched in the immune response, type I interferon signaling pathways, interferon-γ mediated signaling pathways, and so forth.