Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies.

Magdalena Niegowska,Leonardo A Sechi,Daniela Paccagnini,Clara Targhetta,Carla Mannu,Marco Songini

doi:10.1155/2016/5842701

Magdalena Niegowska, Leonardo A Sechi + Show 4 more

Open Access

https://doi.org/10.1155/2016/5842701

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Abstract

As numerous studies put in evidence the increasing incidence of type 1 diabetes (T1D) in children, an early diagnosis is of great importance to define correct treatment and diet. Currently, the identification of classical islet autoantibodies is the primary biomarker for diagnosis in subjects at risk, especially in pediatric patients. Recent studies suggest that detection of antibodies against ZnT8 protein in preclinical phase can predict the development of T1D. We previously demonstrated a significant association of Mycobacterium avium subspecies paratuberculosis (MAP) with T1D in adult Sardinian patients. To enforce this finding, we investigated the presence of antibodies against ZnT8 and proinsulin (PI) with respective homologous epitopes: MAP3865c133–141/ZnT8186–194, MAP3865c125–133/ZnT8178–186, MAP2404c70–85/PI46–61, and MAP1,4αgbp157–173/PI64–80, in 23 children at risk for T1D, formerly involved in the TRIGR study, and 22 healthy controls (HCs). Positivity to anti-MAP and homologous human peptides was detected in 48% of at-risk subjects compared to 5,85% HCs, preceding appearance of islet autoantibodies. Being MAP easily transmitted to humans with infected cow's milk and detected in retail infant formulas, MAP epitopes could be present in extensively hydrolyzed formula and act as antigens stimulating β-cell autoimmunity.

Highlights

Type 1 diabetes (T1D) is an autoimmune disease with increasing incidence in youth worldwide [1], characterized by impaired glucose tolerance progressing to hyperglycemia, which results from T-cell mediated pancreatic β-cell destruction and from a simultaneous production of antibodies (Abs) against islet cells
As numerous studies put in evidence the increasing incidence of diabetes in children, an early diagnosis is of great importance to define a correct method of restraining disease development and to establish ulterior treatment
Environmental factors seem to be critical in the pathogenesis of diabetes and include diet, infectious agents, and perinatal and psychosocial conditions that vary among countries [36]

Summary

Introduction

Type 1 diabetes (T1D) is an autoimmune disease with increasing incidence in youth worldwide [1], characterized by impaired glucose tolerance progressing to hyperglycemia, which results from T-cell mediated pancreatic β-cell destruction and from a simultaneous production of antibodies (Abs) against islet cells. This process starts in early infancy and can occur over many years during childhood without developing clinical symptoms. Despite detection of two or more islet autoantibodies in 13,4% of children in the hydrolyzed formula group, a similar result was obtained for infants weaned to the conventional formula (11,4%), confirming that the formula type has no role in preventing or delaying the onset of autoimmune diabetes

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