Human interferon regulatory factor 5 homologous epitopes ofEpstein-Barrvirus andMycobacterium aviumsubsp.paratuberculosisinduce a specific humoral and cellular immune response in multiple sclerosis patients

Cossu, Davide; Mameli, Giuseppe; Galleri, Grazia; Cocco, Eleonora; Masala, Speranza; Frau, Jessica; Marrosu, Maria Giovanna; Manetti, Roberto; Sechi, Leonardo Antonio

doi:10.1177/1352458514557304

Cited by 38 publications

(62 citation statements)

References 38 publications

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“…Molecular mimicry and SLC11A1 associations are central to this association as well (40, 41). MAP has been associated with Epstein–Barr virus (EBV – thought to be one of the triggers of MS) (44): peptides of each microorganism (MAP and EBV) cross react with anti-myelin basic protein (MBP) (43) and interferon regulatory factor 5 (IRF5) in MS patients (48). Interferon-beta therapy influence antibody response against MAP (49).…”

Section: Map and Multiple Sclerosismentioning

confidence: 99%

Mycobacterium avium ss. paratuberculosis Zoonosis – The Hundred Year War – Beyond Crohn’s Disease

2015

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The factitive role of Mycobacterium avium ss. paratuberculosis (MAP) in Crohn’s disease has been debated for more than a century. The controversy is due to the fact that Crohn’s disease is so similar to a disease of MAP-infected ruminant animals, Johne’s disease; and, though MAP can be readily detected in the infected ruminants, it is much more difficult to detect in humans. Molecular techniques that can detect MAP in pathologic Crohn’s specimens as well as dedicated specialty labs successful in culturing MAP from Crohn’s patients have provided strong argument for MAP’s role in Crohn’s disease. Perhaps more incriminating for MAP as a zoonotic agent is the increasing number of diseases with which MAP has been related: Blau syndrome, type 1 diabetes, Hashimoto thyroiditis, and multiple sclerosis. In this article, we debate about genetic susceptibility to mycobacterial infection and human exposure to MAP; moreover, it suggests that molecular mimicry between protein epitopes of MAP and human proteins is a likely bridge between infection and these autoimmune disorders.

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Section: Map and Multiple Sclerosismentioning

confidence: 99%

Mycobacterium avium ss. paratuberculosis Zoonosis – The Hundred Year War – Beyond Crohn’s Disease

2015

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“…These MAP antigens are considered to be a weapon to impair the most powerful host cellular immunological defenses and to achieve chronic infection in cattle [35]. The phenomenon that stimulates host Th1 and Th2 in different stages of infection [18] is very similar to that in human leprosy [38, 39]. …”

Section: Discussionmentioning

confidence: 99%

“…Experimental CD-type colitis induced with the MAP antigen also suggests the potency of MAP to induce CD [4]. MAP was also linked with others autoimmune diseases such as type 1 diabetes, multiple sclerosis, and Hashimoto's thyroiditis [15–18]. …”

Section: Introductionmentioning

confidence: 99%

Mycobacterium avium Subsp. paratuberculosis Induces Specific IgE Production in Japanese People with Allergies

Cossu

Otsubo

Otsubo³

et al. 2017

International Journal of Inflammation

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Background. The prevalence of allergies is steadily increasing worldwide; however, the pathogenesis is still unclear. We hypothesized that Mycobacterium avium subsp. paratuberculosis (MAP) may contribute to allergy development. This organism can be present in dairy foods, it can elicit an immunomodulatory switch from a Th1 to a Th2 response, and it has been speculated that it is linked to several human autoimmune diseases. To determine the contribution, sera from 99 individuals with various atopic disorders and 45 healthy nonallergic controls were assessed for total IgE levels and successively for MAP-specific IgE by ELISA. Results. The mean total serum IgE level in allergic patients was 256 ± 235 IU/mL, and in the healthy controls it was 62 ± 44 IU/mL (AUC = 0.88; p < 0.0001). Among the patient groups, 50 of the 99 subjects had increased IgE total level ≥ 150 IU/mL, while 49 subjects had IgE ≤ 150 IU/mL (mean level: 407 ± 256 IU/mL versus 106 ± 16 IU/mL; p < 0.0001). Additionally, 6 out of 50 subjects (12%) with IgE ≥ 150 IU/mL and none (0%) with IgE ≤ 150 IU/mL were positive for specific MAP IgE (AUC = 0.63; p = 0.03). Conclusion. The present study revealed that MAP has the ability to induce specific IgE and might contribute to the induction of allergic inflammation in genetically predisposed individuals.

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“…BAFF plays an essential role in B cell homeostasis and has been associated with different types of autoimmune diseases. In recent years, Mycobacterium avium subspecies paratuberculosis (MAP) has been associated to MS in Sardinia-an island with particularly high prevalence of the disease (Frau et al 2013;Mameli et al 2014;Cossu et al 2015). We previously reported that IFN-β enhances the immunological response against MAP .…”

Section: Main Textmentioning

confidence: 98%

Soluble BAFF Level Is Not Correlated to Mycobacterium avium Subspecies Paratuberculosis Antibodies and Increases After Interferon-β Therapy in Multiple Sclerosis Patients

et al. 2016

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B cells are being recognized as one of the major players in the pathogenesis of multiple sclerosis (MS). The B cell activating factor (BAFF) system plays an essential role in B cell homeostasis and function in the periphery. Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to MS in Sardinia. Antibodies against a MAP surface protein, MAP_2694, have been found significantly associated to MS patients, and this response was modified by interferon-β therapy. Increased BAFF levels following IFN-β therapy have been also described in MS patients. In this study, we evaluated whether soluble BAFF levels are comparable in men and women affected by MS and performed a correlation of the reported BAFF increase in MS patients under IFN-β therapy with changes of humoral response against MAP_2694. For these reasons, we investigated 44 MS patients before and after IFN-β therapy. A significant difference of BAFF levels was found between men and women with MS; moreover, we confirmed that IFN-β therapy strongly induces BAFF serum levels, but this was not related to the modification of immunological response against MAP_2694. In conclusion, our study highlights that IFN-β therapy induces the potent B cell survival factor BAFF without alterations of the humoral immune response against MAP.

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Human interferon regulatory factor 5 homologous epitopes ofEpstein-Barrvirus andMycobacterium aviumsubsp.paratuberculosisinduce a specific humoral and cellular immune response in multiple sclerosis patients

Abstract: Our data demonstrated that both EBV and MAP epitopes elicit a consistent humoral response in MS patients compared to HCs, and that the aforementioned peptides are able to induce a T-cell-mediated response that is MS correlated.

Cited by 38 publications

References 38 publications

Mycobacterium avium ss. paratuberculosis Zoonosis – The Hundred Year War – Beyond Crohn’s Disease

Mycobacterium avium ss. paratuberculosis Zoonosis – The Hundred Year War – Beyond Crohn’s Disease

Mycobacterium avium Subsp. paratuberculosis Induces Specific IgE Production in Japanese People with Allergies

Soluble BAFF Level Is Not Correlated to Mycobacterium avium Subspecies Paratuberculosis Antibodies and Increases After Interferon-β Therapy in Multiple Sclerosis Patients

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