Recognition of zinc transporter 8 and MAP3865c homologous epitopes by new-onset type 1 diabetes children from continental Italy

Abstract

There are several pieces of evidence indicating that Mycobacterium avium subspecies paratuberculosis (MAP) infection is linked to type 1 diabetes (T1D) in Sardinian patients. An association between MAP and T1D was recently observed in an Italian cohort of pediatric T1D individuals, characterized by a different genetic background. It is interesting to confirm the prevalence of anti-MAP antibodies (Abs) in another pediatric population from continental Italy, looking at several markers of MAP presence. New-onset T1D children, compared to age-matched healthy controls (HCs), were tested by indirect enzyme-linked immunosorbent assay for the presence of Abs toward the immunodominant MAP3865c/ZnT8 homologues epitopes, the recently identified C-terminal MAP3865c281-287 epitope and MAP-specific protein MptD. Abs against MAP and ZnT8 epitopes were more prevalent in the sera of new-onset T1D children compared to HCs. These findings support the view that MAP3865c/ZnT8 cross-reactivity is involved in the pathogenesis of T1D, and addition of Abs against these peptides to the panel of existing T1D biomarkers should be considered. It is important now to investigate the timing of MAP infection during prospective follow-up in at-risk children to elucidate whether Ab-titers against these MAP/ZnT8 epitopes are present before T1D onset and if so if they wane after diagnosis.

Lack of humoral response against Helicobacter pylori peptides homologous to human ZnT8 in Hashimoto’s thyroiditis patients

“…Both human peptides, which derive from zinc transporter 8 protein, are known to be linked to HT and T1D [1][2][3].…”

“…We investigated whether HP might play a role in HT disease, probably acting through a molecular mimicry mechanism which targets human ZnT8 protein as it was reported for MAP [1][2][3]. We aimed to find an explanation accounting for the interconnection found between HP infection and two autoimmune diseases, HT and T1D [11], which have been proven to be associated with MAP infection [1][2][3].…”

“…We aimed to find an explanation accounting for the interconnection found between HP infection and two autoimmune diseases, HT and T1D [11], which have been proven to be associated with MAP infection [1][2][3].…”

“…Autoimmune diseases, such as Hashimoto's thyroiditis (HT) and type 1 diabetes (T1D), stem from the interaction of genetic susceptibility and environmental exposures [1][2][3][4]. A distinctive marker of HT is the presence of autoantibodies (aAbs) against thyroglobulin (Tg), thyroperoxidase (TPO), and thyrotropin receptor (TR) [5].…”

“…paratuberculosis (MAP) infection/seroprevalence and autoimmune diseases such as T1D and HT was recently demonstrated [1]. Researchers found a very strong humoral response mounted against epitopes belonging to one MAP membrane protein (MAP3865c), and against the homologous region present in human ZnT8, which is a relevant T1D autoantigen specifically expressed in the pancreatic β-cell and in the cubical epithelium that lines thyroid follicles [1][2][3].…”