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.
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.
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.
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.