Specific IgG Response against Mycobacterium avium paratuberculosis in Children and Adults with Crohn’s Disease

Verdier, Julien; Deroche, Louis; Allez, Matthieu; Loy, Caroline; Biet, Franck; Bodier, Christelle; Bay, Sylvie; Ganneau, Christelle; Matysiak‐Budnik, Tamara; Reyrat, Jean Marc; Heyman, Martine; Cerf‐Bensussan, Nadine; Ruemmele, Frank M; Ménard, Sandrine

doi:10.1371/journal.pone.0062780

Cited by 14 publications

(11 citation statements)

References 53 publications

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“…The two studies (four lines) that reported results from sodium dodecyl sulfate (SDS) immunoblot had an overall OR of 25·01 (95% CI 12·55–49·85, I 2 = 43%; Table 2). Four other studies reported significant associations with reactivity to M. paratuberculosis [75–78], four reported no significant association [79–82] and one reported contradictory associations between children and adults with CD [83] (Table 2). Three studies were excluded from this summary because no reaction to M. paratuberculosis occurred [63], only CD patients were tested [84] and results were not reported separately for CD and ulcerative colitis patients [85].…”

Section: Resultsmentioning

confidence: 99%

The zoonotic potential ofMycobacterium aviumssp.paratuberculosis: a systematic review and meta-analyses of the evidence

et al. 2015

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This systematic review-meta-analysis appraises and summarizes all the available research (128 papers) on the zoonotic potential of Mycobacterium avium ssp. paratuberculosis. The latter has been debated for a century due to pathogenic and clinical similarities between Johne's disease in ruminants and Crohn's disease (108 studies) in humans and recently for involvement in other human diseases; human immunodeficiency virus (HIV) infection (2), sarcoidosis (3), diabetes mellitus type 1 (T1DM) (7) and type 2 (3), multiple sclerosis (5) and Hashimoto's thyroiditis (2). Meta-analytical results indicated a significant positive association, consistently across different laboratory methods for Crohn's disease [odds ratio (OR) range 4·26-8·44], T1DM (OR range 2·91-9·95) and multiple sclerosis (OR range 6·5-7·99). The latter two and the thyroiditis hypothesis require further investigation to confirm the association. Meta-regression of Crohn's disease studies using DNA detection methods indicated that choice of primers and sampling frame (e.g. general population vs. hospital-based sample) explained a significant proportion of heterogeneity. Other epidemiological studies demonstrated a lack of association between high-risk occupations and development of Crohn's disease. Due to knowledge gaps in understanding the role of M. paratuberculosis in the development or progression of human disease, the evidence at present is not strong enough to inform the potential public health impact of M. paratuberculosis exposure.

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Section: Resultsmentioning

confidence: 99%

The zoonotic potential ofMycobacterium aviumssp.paratuberculosis: a systematic review and meta-analyses of the evidence

et al. 2015

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“…For faecal IgA and polymeric immunoglobulin receptor (pIgR) assays, faecal proteins were extracted mechanically in complete antiprotease cocktail (Roche) and frozen at −80 °C. IgA and pIgR concentrations were measured as described previously with sheep anti-mouse IgA (Sigma) or for coating and horseradish-peroxidase (HRP)-conjugated goat anti-mouse IgA (Sigma) for revelation 64 .…”

Section: Methodsmentioning

confidence: 99%

Gut dysbiosis and impairment of immune system homeostasis in perinatally-exposed mice to Bisphenol A precede obese phenotype development

Malaisé

Ménard

Cartier

et al. 2017

Sci Rep

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Epidemiology evidenced the Bisphenol A (BPA), a chemical found in daily consumer products, as an environmental contributor to obesity and type II diabetes (T2D) in Humans. However, the BPA-mediated effects supporting these metabolic disorders are still unknown. Knowing that obesity and T2D are associated with low-grade inflammation and gut dysbiosis, we performed a longitudinal study in mice to determine the sequential adverse effects of BPA on immune system and intestinal microbiota that could contribute to the development of metabolic disorders. We observed that perinatal exposure to BPA (50 µg/kg body weight/day) induced intestinal and systemic immune imbalances at PND45, through a decrease of Th1/Th17 cell frequencies in the lamina propria concomitant to an increase of splenic Th1/Th17 immune responses. These early effects are associated with an altered glucose sensitivity, a defect of IgA secretion into faeces and a fall of faecal bifidobacteria relative to control mice. Such BPA-mediated events precede infiltration of pro-inflammatory M1 macrophages in gonadal white adipose tissue appearing with ageing, together with a decreased insulin sensitivity and an increased weight gain. Our findings provide a better understanding of the sequential events provoked by perinatal exposure to BPA that could support metabolic disorder development in later life.

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“…In the last years, analyses of mycobacterial genomes permitted to indentify the production of lipopentapeptide (L5P) in MAP as a distinctive feature among subspecies [ 13 ]. Studies in MAP-infected ruminants showed a strong immunogenicity of L5P [ 14 ] and, more recently, highly specific IgG responses to L5P were verified in patients affected by Crohn’s disease [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Seroreactivity against Specific L5P Antigen from Mycobacterium avium subsp. paratuberculosis in Children at Risk for T1D

et al. 2016

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Aims/HypothesisAlthough numerous environmental agents have been investigated over the years as possible triggers of type 1 diabetes (T1D), its causes remain unclear. We have already demonstrated an increased prevalence of antibodies against peptides derived from Mycobacterium avuim subsp. paratuberculosis (MAP) homologous to human zinc transporter 8 protein (ZnT8) and proinsulin in Italian subjects at risk for or affected by T1D. In this study, we compared titers of the previously detected antibodies with seroreactivity to MAP lipopentapetide (L5P) that recently emerged as a strong immunogenic component able to specifically distinguish MAP from other mycobacteria.MethodsPlasma of 32 children and youth at risk for T1D including follow-up samples and 42 age-matched healthy controls (HC) recruited at the Tor Vergata University Hospital in Rome was analyzed by indirect ELISA for the presence of antibodies against MAP-derived epitopes MAP3865c133–141, MAP3865c125-133, MAP2404c70-85 and MAP1,4αgbp157-173 along with their ZnT8 and proinsulin homologs. The data were analyzed through two-tailed Mann-Whitney U test and relation between variables was determined by principal component analysis.ResultsResponses to L5P were not detectable in subjects whose initial seroreactivity to MAP peptides and their human homologs was lost in follow-up samples, whereas anti-L5P antibodies appeared constantly in individuals with a stable immunity against MAP antigens. The overall coincidence in positivity to L5P and the four MAP epitopes both in children at risk for T1D and HC exceeded 90%.ConclusionsMAP-derived homologs may cross-react with ZnT8 and proinsulin peptides inducing immune responses at a young age in subjects predisposed for T1D. Thus, L5P may have a diagnostic value to immediately indicate the presence of anti-MAP seroreactivity when evaluation of a more complex antibody status is not required. Almost complete coincidence in responses to both types of antigens lends support to the involvement of MAP in T1D.

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Specific IgG Response against Mycobacterium avium paratuberculosis in Children and Adults with Crohn’s Disease

Cited by 14 publications

References 53 publications

The zoonotic potential ofMycobacterium aviumssp.paratuberculosis: a systematic review and meta-analyses of the evidence

The zoonotic potential ofMycobacterium aviumssp.paratuberculosis: a systematic review and meta-analyses of the evidence

Gut dysbiosis and impairment of immune system homeostasis in perinatally-exposed mice to Bisphenol A precede obese phenotype development

Seroreactivity against Specific L5P Antigen from Mycobacterium avium subsp. paratuberculosis in Children at Risk for T1D

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