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Proinsulin and MAP3865c homologous epitopes are a target of antibody response in new‐onset type 1 diabetes children from continental Italy
Author(s) -
Masala Speranza,
Cossu Davide,
Piccinini Simona,
Rapini Novella,
Mameli Giuseppe,
Manca Bitti Maria Luisa,
Sechi Leonardo A
Publication year - 2015
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.12269
Subject(s) - proinsulin , epitope , medicine , population , immunology , antibody , asymptomatic , endocrinology , diabetes mellitus , environmental health
Mycobacterium avium subspecies paratuberculosis ( MAP ) asymptomatic infection is speculated to play a role in type 1 diabetes ( T1D ) among Sardinian subjects. Data obtained analyzing a pediatric population from mainland Italy lends support to the hypothesis, which envisions MAP as an environmental factor at play in T1D pathogenesis. Aiming to investigate the likelihood of cross‐recognition between linear determinants shared by self (proinsulin) and non‐self ( MAP ) proteins, 59 children with new onset T1D and 60 healthy controls ( HCs ) from continental Italy were enrolled in the study. Serum samples were subjected to indirect enzyme‐linked immunosorbent assay ( ELISA ) for the presence of antibodies (Abs) toward four homologues MAP /proinsulin epitopes. The rate of MAP infection (42.4% in T1D children and 5% in HCs ; p < 0.0001) was estimated searching for Abs against MAP specific protein MptD . The homologous MAP 2404c 70 ‐ 85 and proinsulin ( PI ) 46 ‐ 61 peptides were recognized by 42.4 and 39% of new‐onset T1D children and only in 5% of HCs ( AUC = 0.76, AUC = 0.7, p < 0.0001); whereas the prevalence of Abs against MAP 1,4‐α‐gbp 157 ‐ 173 and PI 64 –80 peptides was 45.7 and 49.1% in new‐onset T1D children, respectively, compared with 3.3% of HCs ( AUC = 0.74 and p < 0.0001 in both). Pre‐incubation of MAP Ab‐positive sera with proinsulin peptides was able to block the binding to the correspondent MAP epitopes, thus showing that Abs against these homologous peptides are cross‐reactive. MAP /Proinsulin Ab mediated cross‐recognition, most likely via molecular mimicry, maybe a factor in accelerating and/or initiating T1D in MAP ‐infected children. Indeed, it is known that anti‐proinsulin and anti‐Insulin autoantibodies are the earliest to appear.