Abstract

Mycobacterium avium subspecies paratuberculosis (MAP) asymptomatic infection has been previously linked to Type 1 diabetes (T1D) and Multiple Sclerosis. An association between MAP infection and Hashimoto's thyroiditis (HT) was also proposed only in a case report. This study aimed to investigate the robustness of the latter association, testing a large cohort of HT and healthy control (HCs) subjects, all from Sardinia. Prevalence of anti-MAP3865c Abs was assessed by indirect enzyme-linked immunosorbent assay (ELISA). Moreover, given that human ZnT8 is specifically expressed in the pancreatic β-cells, in the follicle epithelial cells and in the parafollicular cells of the thyroid gland, we also tested ZnT8 epitopes homologues to the MAP3865c immunodominant peptides previously identified. Indeed, Abs targeting MAP3865c and ZnT8 homologous regions display similar frequencies in patients and controls, thus suggesting that Abs recognizing these epitopes could be cross-reactive. A statistically significant difference was found between HT patients and HCs when analyzing the humoral response mounted against MAP3865c/ZnT8 homologues epitopes. To our knowledge, this is the first report, which provides statistically significant evidence sustaining the existence of an association between MAP sero-reactivity and HT. Further studies are required to investigate the relevance of MAP to HT, aimed at deciphering if this pathogen can be at play in triggering this autoimmune disease. Likewise, genetic polymorphism of the host, and other environmental factors need to be investigated.

Highlights

  • Hashimoto’s thyroiditis (HT) is a chronic inflammatory condition affecting the thyroid gland

  • It has been proposed that Mycobacterium avium subspecies paratuberculosis (MAP) may be one of the environmental factor at play in triggering HT disease [4,5], but the assumption made was not supported by statistically significant data

  • We investigated whether MAP3865c/ZnT8 homologues peptides, which were highly immunogenic in type 1 diabetes (T1D) subjects, could be recognized by HT Sardinian patients

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Summary

Introduction

Hashimoto’s thyroiditis (HT) is a chronic inflammatory condition affecting the thyroid gland. The hallmark of this disease is the abundant lymphocyte B and T infiltrate, resulting in thyroid destruction. It involves both humoral and cellular responses against two thyroid autoantigens: thyroid peroxidase (TPO) and thyroglobulin (TG) [1]. HT is a multifactorial disease stemming from an interaction between genetic and environmental risk factors [2,3]. It has been proposed that Mycobacterium avium subspecies paratuberculosis (MAP) may be one of the environmental factor at play in triggering HT disease [4,5], but the assumption made was not supported by statistically significant data. MAP colonizes the mucosa-associated lymphoid tissue (MALT) of the small intestine, where it resides inside the intraepithelial macrophages [6] causing Johne’s disease (JD) in ruminants [7] and it is associated with Crohn’s disease (CD) in humans [8]; it has been linked to some extradigestive diseases such as type 1 diabetes (T1D) [9,10,11] and multiple

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