Proinsulin and MAP3865c homologous epitopes are a target of antibody response in new-onset type 1 diabetes children from continental Italy.
Pediatr Diabetes
; 16(3): 189-95, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25720593
ABSTRACT
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 MAP2404c70-85 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-gbp157-173 and PI64-80 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.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proinsulina
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Mycobacterium avium subsp. paratuberculosis
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Diabetes Mellitus Tipo 1
Tipo de estudio:
Observational_studies
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Risk_factors_studies
Límite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Male
País como asunto:
Europa
Idioma:
En
Año:
2015
Tipo del documento:
Article