<i>Mycobacterium avium</i>subsp.<i>paratuberculosis</i>in an Italian Cohort of Type 1 Diabetes Pediatric Patients

Bitti, Maria Luisa Manca; Masala, Speranza; Capasso, F.; Rapini, Novella; Piccinini, Simona; Angelini, Federica; Pierantozzi, Andrea; Lidano, Roberta; Pietrosanti, Silvia; Paccagnini, Daniela; Sechi, Leonardo Antonio

doi:10.1155/2012/785262

Cited by 29 publications

(19 citation statements)

References 24 publications

(46 reference statements)

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“…Several factors, such as genetic isolation, have likely contributed to the fixing of predisposing alleles. MAP infection is estimated to affect approximately 60% of Sardinian herds [6], and this mycobacterium can be found in pasteurized milk products and may be asymptomatically transmitted to humans [8]. Due to the potential role played by MAP in T1D pathogenesis, it is relevant to better characterize the prevalence of anti-MAP Abs in the Sardinian population.…”

Section: Introductionmentioning

confidence: 99%

Zinc Transporter 8 and MAP3865c Homologous Epitopes are Recognized at T1D Onset in Sardinian Children

Masala

Zedda²,

Cossu

et al. 2013

PLoS ONE

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Our group has recently demonstrated that Mycobacterium avium subspecies paratuberculosis (MAP) infection significantly associates with T1D in Sardinian adult patients. Due to the potential role played by MAP in T1D pathogenesis, it is relevant to better characterize the prevalence of anti-MAP antibodies (Abs) in the Sardinian population, studying newly diagnosed T1D children. Therefore, we investigated the seroreactivity against epitopes derived from the ZnT8 autoantigen involved in children at T1D onset and their homologous sequences of the MAP3865c protein. Moreover, sera from all individuals were tested for the presence of Abs against: the corresponding ZnT8 C-terminal region, the MAP specific protein MptD, the T1D autoantigen GAD65 and the T1D unrelated Acetylcholine Receptor. The novel MAP3865c281–287 epitope emerges here as the major C-terminal epitope recognized. Intriguingly ZnT8186–194 immunodominant peptide was cross-reactive with the homologous sequences MAP3865c133–141, strengthening the hypothesis that MAP could be an environmental trigger of T1D through a molecular mimicry mechanism. All eight epitopes were recognized by circulating Abs in T1D children in comparison to healthy controls, suggesting that these Abs could be biomarkers of T1D. It would be relevant to investigate larger cohorts of children, followed over time, to elucidate whether Ab titers against these MAP/Znt8 epitopes wane after diagnosis.

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Section: Introductionmentioning

confidence: 99%

Zinc Transporter 8 and MAP3865c Homologous Epitopes are Recognized at T1D Onset in Sardinian Children

Masala

Zedda²,

Cossu

et al. 2013

PLoS ONE

Self Cite

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“…The association of MAP with T1DM has been reported in Sardinia, known to have a high prevalence of type 1 diabetes and a high rate of MAP infection among sheep and cattle [6][7][8]19,27]. However, Rani et al could not find any association despite the high prevalence of MAP and T1DM in India, probably due to the low number of patients investigated [21] or the genetic predisposition of the infected population in developing such an autoimmunity.…”

Section: Discussionmentioning

confidence: 97%

“…Recent studies have suggested that Mycobacterium avium subsp. paratuberculosis (MAP) is associated with T1DM [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Detection of Mycobacterium avium subsp. paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA

Shariati

Alaei²,

Keshavarz

et al. 2016

J Infect Dev Ctries

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Introduction: Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis or Johne's disease in ruminants. Its role in triggering autoimmunity, including type 1 diabetes mellitus (T1DM), has been reported in recent years. Due to the high contamination rate of MAP in Iran's livestock and the increasing outbreak of T1DM, we investigated this association in a small group of patients with T1DM in Iran. Methodology: Blood samples of 29 T1DM patients and 29 healthy control subjects were tested through enzyme-linked immunosorbent assay (ELISA) to detect antibodies against MAP3865c and ZnT8 homologous epitopes and the presence of MAP DNA. Blood samples were also cultured in mycobacterial growth indicator tubes and Herrold's egg yolk medium containing mycobactin J. Results: The results of ELISA showed a significant difference between T1DM patients and healthy group. IS900 was also detected in 51.72% of T1DM patients but in none of the control group. None of the samples grew in culture media. Conclusions: Due to the presence of MAP DNA and antibodies against MAP peptides in a significant number of T1DM patients compared with healthy control subjects, we may consider MAP as a possible trigger of T1DM in Iran. This indicates that exposure to MAP occurred in the positive subjects. Identifying the sources of contamination and routes of MAP transmission to humans seems necessary to prevent and reduce the burden of MAP infection in Iran.

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“…It has been proposed that MAP is the source of mycobacterial HSP65 and thus an environmental trigger for T1D. A large and increasing body of work has subsequently solidified the association of MAP and T1D [83,[108][109][110][111][112][113][114][115][116][117][118][119][120][121]. These studies have also confirmed genetic factors linking risk for MAP and T1D [63].…”

Section: Map Bcg and Autoimmune Diabetesmentioning

confidence: 89%

Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

Dow

2020

Microorganisms

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Bacille Calmette–Guerin (BCG) vaccination is widely practiced around the world to protect against the mycobacterial infection tuberculosis. BCG is also effective against the pathogenic mycobacteria that cause leprosy and Buruli’s ulcer. BCG is part of the standard of care for bladder cancer where, when given as an intravesicular irrigant, BCG acts as an immunomodulating agent and lessens the risk of recurrence. Mycobacterium avium ss. paratuberculosis (MAP) causes a fatal enteritis of ruminant animals and is the putative cause of Crohn’s disease of humans. MAP has been associated with an increasingly long list of inflammatory/autoimmune diseases: Crohn's, sarcoidosis, Blau syndrome, Hashimoto’s thyroiditis, autoimmune diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis, lupus and Parkinson’s disease. Epidemiologic evidence points to BCG providing a “heterologous” protective effect on assorted autoimmune diseases; studies using BCG vaccination for T1D and MS have shown benefit in these diseases. This article proposes that the positive response to BCG in T1D and MS is due to a mitigating action of BCG upon MAP. Other autoimmune diseases, having a concomitant genetic risk for mycobacterial infection as well as cross-reacting antibodies against mycobacterial heat shock protein 65 (HSP65), could reasonably be considered to respond to BCG vaccination. The rare autoimmune disease, relapsing polychondritis, is one such disease and is offered as an example. Recent studies suggesting a protective role for BCG in Alzheimer’s disease are also explored. BCG-induced energy shift from oxidative phosphorylation to aerobic glycolysis provides the immunomodulating boost to the immune response and also mitigates mycobacterial infection—this cellular mechanism unifies the impact of BCG on the disparate diseases of this article.

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Mycobacterium aviumsubsp.paratuberculosisin an Italian Cohort of Type 1 Diabetes Pediatric Patients

Cited by 29 publications

References 24 publications

Zinc Transporter 8 and MAP3865c Homologous Epitopes are Recognized at T1D Onset in Sardinian Children

Zinc Transporter 8 and MAP3865c Homologous Epitopes are Recognized at T1D Onset in Sardinian Children

Detection of Mycobacterium avium subsp. paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA

Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

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