Type 1 Diabetes at-risk children highly recognize Mycobacterium avium subspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin.

Magdalena Niegowska,Giuseppe Mameli,Simona Piccinini,Maria Luisa Manca Bitti,Elisa Caggiu,Leonardo A Sechi,Novella Rapini

doi:10.1038/srep22266

Magdalena Niegowska, Giuseppe Mameli + Show 5 more

Open Access

https://doi.org/10.1038/srep22266

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Abstract

Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to T1D as a putative environmental agent triggering or accelerating the disease in Sardinian and Italian populations. Our aim was to investigate the role of MAP in T1D development by evaluating levels of antibodies directed against MAP epitopes and their human homologs corresponding to ZnT8 and proinsulin (PI) in 54 T1D at-risk children from mainland Italy and 42 healthy controls (HCs). A higher prevalence was detected for MAP/ZnT8 pairs (62,96% T1D vs. 7,14% HCs; p < 0.0001) compared to MAP/PI epitopes (22,22% T1D vs. 9,52% HCs) and decreasing trends were observed upon time-point analyses for most peptides. Similarly, classical ZnT8 Abs and GADA decreased in a time-dependent manner, whereas IAA titers increased by 12%. Responses in 0–9 year-old children were stronger than in 10–18 age group (75% vs. 69,1%; p < 0.04). Younger age, female sex and concomitant autoimmune disorders contributed to a stronger seroreactivity suggesting a possible implication of MAP in multiple autoimmune syndrome. Cross-reactivity of the homologous epitopes was reflected by a high correlation coefficient (r2 > 0.8) and a pairwise overlap of positivity (>83% for MAP/ZnT8).

Highlights

Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to type 1 diabetes (T1D) as a putative environmental agent triggering or accelerating the disease in Sardinian and Italian populations
We investigated whether the Abs pattern involving sero-reactivity to MAP-derived peptides and their human zinc transporter 8 (ZnT8)/PI homologs in children and youth at risk for T1D from mainland Italy reflects prevalences reported for new-onset T1D Sardinian and Italian pediatric patients[4,11]
Among 54 subjects at risk of T1D, 70,37% (n = 38) resulted positive to at least one of the eight assessed peptides compared to 16,67% (n = 7) of healthy controls (HCs). 78,95% (n = 30) of the positive at-risk children had Abs targeting not less than four epitopes, 11,11% of whom were fully responsive to all peptide pairs

Summary

Introduction

Our aim was to investigate the role of MAP in T1D development by evaluating levels of antibodies directed against MAP epitopes and their human homologs corresponding to ZnT8 and proinsulin (PI) in 54 T1D at-risk children from mainland Italy and 42 healthy controls (HCs). Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to T1D as a putative environmental agent triggering or accelerating the disease in Sardinian and Italian populations[2,3,4,5,6]. Considering the estimates that MAP infections among cattle herds in Sardinia are of high frequency reaching 60%17, exposure to MAP of an external population would occur with minor intensity providing an important ground for comparison of the two cohorts

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