Distinct Antibody Signatures to Human Endogenous Retroviruses and Mycobacterium Paratuberculosis in Newly Diagnosed Tunisian Type 1 Diabetes Patients

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells. Environmental factors are widely considered to play a major role in the pathophysiology of T1D. Mycobacterium avium subspecies paratuberculosis (MAP) has been proposed as a potential T1D trigger based on the molecular mimicry mechanism and immune cross-reactivity with pancreatic autoantigens. Furthermore, several lines of evidence have recently highlighted the crucial role of Human Endogenous Retroviruses (HERVs) reactivation in multiple autoimmune diseases. Previous studies have demonstrated the presence of antibodies targeting several immunodominant epitopes of MAP and HERV in the serum of T1D patients; however, no data on these antibodies have been reported in Tunisian patients. Therefore, the present study aims to explore the involvement of MAP and HERV in T1D pathology in the Tunisian population. Indirect enzyme-linked immunosorbent assays (ELISA) was performed to evaluate the humoral immune response against MAP epitopes (MAP3865c(125–138), MAP3865c(133–141), MAP2404c(70–85), MAP1,4-α-gbp(157–173)) and their human homologous peptides in Zinc transporter 8 (ZnT8(178–186), ZnT8(186–194)) and in Proinsulin (PI(41−64)). In addition, we measured the antibody response against epitopes derived from the envelope protein of two HERV families (HERV-Wenv(93–108) and HERV-Kenv(19–37)). The ELISA was conducted using the serum of newly diagnosed T1D children (n = 56), their healthy siblings (n = 19), and unrelated healthy controls (n = 23). Our results revealed a high serum prevalence of antibodies against the selected peptides in T1D patients. Interestingly, the humoral immune reactivity was higher in patients with the most acute complication of T1D, Diabetic ketoacidosis. Moreover, antibodies directed against MAP and HERV peptides showed a significant, albeit weak, positive correlation with neutrophil count and neutrophil-to-lymphocyte ratio (NLR). Our findings support the hypothesis that MAP and HERV reactivation may be linked to the onset and severity of T1D.