IFN-α neutralizing antibodies distinguish LADA from early-onset type 1 diabetes

Context: Autoantibodies against IFN-α (AAb-IFN-α) might be associated with the less aggressive autoimmunity in latent autoimmune diabetes in adults (LADA) compared to early-onset type 1 diabetes (T1D). Objective: To investigate the presence and clinical relevance of the positivity to AAb-IFN-α in people with LADA compared to T1D. Research design and methods: Serum levels of AAb against IFN-α isoforms were measured using a cell-based approach in 41 subjects with LADA and in 90 subjects with T1D. Outcomes: The primary and secondary outcomes were the difference between LADA and T1D in the proportion of participants testing positive for AAb against ≥2 and against 3 IFN-α isoforms, respectively. Presence and levels of AAb-IFN-α were related to clinical and biochemical features of participants with LADA. Results: Seven (17.1%) and 5(12.2%) participants with LADA, and 3(3.3%) and 0 participants with T1D showed positivity for AAb against ≥2 and 3 IFN-α isoforms (p=0.011, and p=0.0025, respectively). Fasting blood glucose and HbA1c levels were numerically lower among people with LADA testing positive for AAb against ≥2 IFN-α isoforms, than among those who were either negative or positive for AAb against one IFN-α isoform. Among LADA-positive individuals, levels of AAb against IFN-α2 isoform were inversely correlated with GADA levels (rho= -0.513; p=0.025). Conclusions: Autoimmunity against IFN-α is peculiar to autoimmune diabetes and appears to be distinctive of its slowly progressive forms. Understanding the underlying molecular mechanisms and clinical significance of this novel autoimmunity could lead to the development of new therapeutic strategies in autoimmune diseases, advancing personalized medicine.