Abstract
The etiology of T1D remains unknown, although a variety of etiological agents have been proposed as potential candidates to trigger autoimmunity in susceptible individuals. Emerging evidence has indicated that endogenous human retrovirus (HERV) may play a role in the disease etiopathogenesis; although several epigenetic mechanisms keep most HERVs silenced, environmental stimuli such as infections may contribute to the transcriptional reactivation of HERV-Wand thus promote pathological conditions. Previous studies have indicated that also Mycobacterium avium subspecies paratuberculosis (MAP) could be a potential risk factor for T1D, particularly in the Sardinian population. In the present study, the humoral response against HERV-W envelope and MAP-derived peptides was analyzed to investigate their potential role in T1D etiopathogenesis, in a Sardinian population at T1D onset (n = 26), T1D (45) and an age-matched healthy population (n = 45). For the first time, a high serum-prevalence of anti-Map and anti-HERV-W Abs was observed in pediatric patients at onset of T1D compared to T1D patients and healthy controls. Our results support the hypothesis that external infections and internal reactivations are involved in the etiology of T1D, and that HERV-W activation may be induced by infectious agents such as MAP.
Highlights
Type 1 diabetes (T1D) is an autoimmune disorder afflicting millions of people around the world, characterized by T cell infiltration within pancreatic islets and marked by the production of autoantibodies to the beta-cell [1]
= 0.80; p < 0.0001, Figure 1D); anti-Mycobacterium avium subspecies paratuberculosis (MAP) 1,4-α-gbp 157–173 Abs were detected in patients with onset of T1D (57.69%, 15 out of 26 ) and HCs (8.57%, 3 out of 35); anti-MAP 2404c 70–80 were detected in patients with onset of T1D (61.54%, 16 out of 26) and HCs (8.57%, 3 out of 35)
In recent studies a direct correlation between anti-MAP Abs and anti-human retrovirus (HERV)-Wenv has been observed in a cohort of patient with T1D [28]
Summary
Type 1 diabetes (T1D) is an autoimmune disorder afflicting millions of people around the world, characterized by T cell infiltration within pancreatic islets and marked by the production of autoantibodies to the beta-cell [1]. The major genetic determinant of T1D are polymorphisms within the HLA region [3], over 60 non-HLA loci. T1D susceptibility loci have been identified [4]. The genetic drift alone cannot explain the increase in the incidence of T1D, and environmental factors are thought to play a critical role in triggering islet autoimmunity [5,6]. A variety of studies suggested that the environmental agents trigger disease development in genetically susceptible subjects [7,8]. A number of factors, including diet, intestinal dysbiosis, viral infections such as enteroviruses (coxsackieviruses, rotaviruses, cytomegalovirus, parvovirus), have been explored as potential risk factor for the disease progression, but no causal relationship has been established [8]
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