Autoantibodies against Proinsulin, Human Endogenous Retrovirus W (HERV-W) and Mycobacterium avium Subspecies Paratuberculosis (MAP) Slowly Decrease Years after T1DM Diagnosis

Abstract

Previous studies have highlighted the potential role of Mycobacterium avium subspecies paratuberculosis (MAP) and human endogenous retrovirus W (HERV-W) in the pathogenesis of type 1 diabetes (T1DM) among Sardinian subjects. To better understand how antibody responses evolve during disease progression, a serological evaluation of IgG antibodies was performed in Sardinian children with T1DM collected at different time-points following the onset of the disease. It is known that anti-PI and anti-insulin (IAA) autoantibodies are the first to appear before the clinical onset of T1DM. In order to investigate the humoral responses, 69 children with T1DM were enrolled in the study, including 25 with new onset, 25 with T1DM at 1–5 years since diagnosis and 19 with T1DM at 6–12 years since diagnosis. Serum samples were tested for the presence of antibodies (Abs) against PI46–61, three MAP epitopes (including MAP 2404c, which has a homologous sequence with PI) and two HERV-W-derived epitopes via indirect enzyme-linked immunosorbent assay (ELISA). The data obtained from the analysis showed significantly higher IgG responses against all peptides detected in the new onset group compared to longer suffering (1–5 and 6–12 years) T1DM patients, also showing a robust correlation between the proinsulin autoantibody and anti-MAP/HERV antibodies, characterized by a progressive decline the first year after onset. Taken together, these findings support the hypothesis that MAP and HERV could act as risk factors for T1DM, suggesting that they may serve as potential biomarkers of disease progression in early-stage T1DM.