DM disease activity correlated significantly with the type I IFN gene signature (r = 0.41, P = 0.007) and with the type I IFN chemokine signature (r = 0.61, P < 0.0001).
IFN-α, a cytokine expressed in human islets from individuals affected by type 1 diabetes, plays a key role in the pathogenesis of diabetes by upregulating inflammation, endoplasmic reticulum (ER) stress and MHC class I overexpression, three hallmarks of islet histology in early type 1 diabetes.
In addition, for G1, Black race, Hispanic ethnicity, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≥ 0.6, ferritin ≥ 350 ng/mL, LDL< 100 mg/dL and diabetes; for G2, BMI ≥ 30 kg/m(2), platelets < 150 K/μL, LDL< 100 mg/dL and the use of PEG-IFN alfa-2b; and for G3, AST/ALT ≥ 1.0, all negatively predicted rapid virological response.
The high T1-IFN signatures of the MDA5 antibody-positive DM patients in serum and deep vasculatures suggested that T1-IFN may have important roles in the vasculopathy of these patients.
The innate immune effects induced by IFNα may induce and amplify the adaptive immune response against human beta cells, indicating that IFNα has a central role in the early phases of diabetes.
These findings identify transient increased expression of type I IFN genes in preclinical diabetes as a risk factor for autoimmunity in children with a genetic predisposition to T1D.
We conducted a retrospective analysis of data obtained from Veterans Administrations Informatics and Computing Infrastructure (VINCI) to identify an adult cohort of patients without diabetes with chronic HCV infection who received Peg-IFN-based therapy between October 2001 and December 2011.