Humoral response against host-mimetic homologous epitopes of Mycobacterium avium subsp. paratuberculosis in Japanese multiple sclerosis patients

Cossu, Davide; Yokoyama, Kazumasa; Sechi, Leonardo Antonio; Otsubo, Shigeru; Tomizawa, Yuji; Momotani, Eiichi

doi:10.1038/srep29227

Cited by 24 publications

(35 citation statements)

References 30 publications

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“…Detection of MAP in 2–4 million patients with ulcerative colitis (UC) has been documented/speculated upon [ 73 ]. However, only 13 research documents considered MAP in connection to UC throughout the study period [ 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. Growth of MAP research linked with UC had a negative growth rate of –30% ( Table 7 ).…”

Section: Resultsmentioning

confidence: 99%

Systematic Assessment of Mycobacterium avium Subspecies Paratuberculosis Infections from 1911–2019: A Growth Analysis of Association with Human Autoimmune Diseases

Ekundayo

Okoh

2020

Microorganisms

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Mycobacterium avium subsp. paratuberculosis (MAP) is an understudied pathogen worldwide with continuous implications in human autoimmune diseases (ADs). The awareness of MAP appears to be low in many places and its research is at infant stage in many countries. The lack of worldwide coverage of the MAP research landscape calls for urgent research attention and prioritization. This present study aimed to assess MAP global research productivity with an emphasis on its implications in ADs via bibliometric and growth analytic frameworks from authors, countries, institutions, international, disciplines and collaboration network perspectives. MAP primary articles were retrieved from the Scopus database and the Web of Science from 1911 to 2019 via title-specific algorithm. Analytic results of dataset yielded a total of 3889 articles from 581 journals and 20.65 average citations per documents. The annual growth rate of MAP research for the period was 6.31%. Based on a country’s productivity (articles (%), freq. of publication (%)), the USA (887 (22.81%), 26.72%), and Australia (236 (6.07%), 6.07%) ranked the top 2 countries but Egypt and Germany had the highest average growth rate (AGR, 170%) in the last 3 years. MAP studies are generally limited to Europe, Australia, Asia, South America and few nations in Africa. It had positive growth rate (30%–100%) in relation to type 1 diabetes mellitus and rheumatoid arthritis ADs; food science and technology, immunology, agriculture, pathology, and research and experimental medicine, wildlife, environments, virulence, disease resistance, meat and meat products, osteopontin, waste milk and slurry/sludge digestion subjects; but negative growth (−130% to −30%) in ulcerative colitis and Parkinson’s disease and no growth in multiple sclerosis, sarcoidosis, thyroid disorders, psoriasis, and lupus. The mapping revealed a gross lack of collaboration networking in terms of authorship, (intra- and inter-) nationally and institutionally with a generalized collaboration index of 1.82. In conclusion, inadequate resources-, knowledge- and scientific-networking hampered growth and awareness of MAP research globally. The study recommends further research to strengthen evidence of MAP’s epidemiologic prevalence in ADs and proffer practical solution(s) for drug development and point-of-care diagnostics amongst other extended themes.

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Section: Resultsmentioning

confidence: 99%

Systematic Assessment of Mycobacterium avium Subspecies Paratuberculosis Infections from 1911–2019: A Growth Analysis of Association with Human Autoimmune Diseases

Ekundayo

Okoh

2020

Microorganisms

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“…Mycobacterium avium subspecies paratuberculosis (MAP) is accepted as the cause of Johne's Disease (JD) [1], a chronic diarrheal wasting disease of cattle and a wasting disease in sheep and goats [2] and has long been suspected to be involved in the etiology of Crohn's Disease (CD), an inflammatory bowel disease (IBD) of humans [3]. MAP and/or CD are also associated with many other autoimmune diseases including multiple sclerosis [4][5][6][7][8][9][10][11][12][13], type I diabetes mellitus [14][15][16][17][18][19], rheumatoid arthritis [20][21][22], Sjogren's syndrome [23], asymmetric lateral sclerosis [24], systemic sclerosis, celiac disease [25], depression [26], thyroiditis [27], and the neurodegenerative diseases including Alzheimer's disease [28] and Parkinson's disease [29]. A diarrheal/wasting illness associated with infection with MAP has also been reported in non-human primates [30].…”

Section: Introductionmentioning

confidence: 99%

Presence Of Infection By Mycobacterium Avium Subsp. Paratuberculosis In The Blood Of Patients With Crohn’s Disease And Control Subjects Shown By Multiple Laboratory Culture And Antibody Methods

Kuenstner¹,

Potula²,

Bull

et al. 2020

Preprint

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Mycobacterium avium subspecies paratuberculosis (MAP) has long been suspected to be involved in the etiology of Crohns disease (CD). An obligate intracellular pathogen, MAP persists and influences host macrophages. The primary goals of this study were to assess the degree of viable culturable MAP bacteremia in humans, definite identification of the organisms cultured and to assess if CD patients have a significantly higher rate of MAP infection compared to controls. A secondary goal was to compare the efficacy of three culture methods plus a phage assay and four antibody assays performed in separate laboratories, to detect MAP from the parallel samples. Culture and serological MAP testing was performed blind on whole blood samples obtained from 201 subjects including 61 CD patients, two patients with CD and concurrent ulcerative colitis (UC), 14 patients with UC only and 140 non-CD controls. Viable MAP bacteremia was detected in a significant number of study subjects across all groups. This included Pozzato culture (124/201 or 62% of all subjects, 35/61 or 57% of CD patients), Phage assay (113/201 or 56% of all subjects, 28/61 or 46% of CD patients), TiKa culture (64/201 or 32% of all subjects, 22/61 or 36% of CD patients) and MGIT culture (36/201 or 18% of all subjects, 15/61 or 25% of CD patients). A link between MAP detection and CD was observed with MGIT culture and one of the antibody methods (Hsp65) confirming previous studies. Other detection methods showed no association between any of the groups tested. Nine subjects with positive Phage assay (8/9) or MAP culture (1/9) were again positive with the Phage assay one year later. This study highlights viable MAP bacteremia is widespread in the study population including CD patients, those with other autoimmune conditions and asymptomatic healthy subjects.

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“…The in silico molecular modeling study demonstrated that the MAP_2694 295–303 peptide displays a binding affinity to MS-associated HLA-DR molecules [10]. Furthermore, a recent article has revealed high serum levels of antibodies against the MAP_2694 295–303 peptide in Japanese patients with MS (12 RRMS, 2 secondary progressive, and 1 primary progressive) and those with a clinically isolated syndrome (CIS) [11].…”

Section: Introductionmentioning

confidence: 99%

Anti-Mycobacterial Antibodies in Paired Cerebrospinal Fluid and Serum Samples from Japanese Patients with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder

Yokoyama

Cossu

Hoshino

et al. 2018

JCM

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Local synthesis of antibodies and presence of oligoclonal bands in the cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS). We investigated the frequency of antibodies against mycobacterial and relevant human epitopes in the CSF of patients with MS or neuromyelitis optica spectrum disorder (NMOSD) and whether these antibodies differed from those present in the serum. Matched serum and CSF samples from 46 patients with MS, 42 patients with NMOSD, and 29 age-matched and sex-matched control subjects were screened retrospectively for the presence of antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) pentapeptide (MAP_5p), MAP_2694295–303, and myelin basic protein (MBP)85–98 peptides by using indirect ELISA. Serum levels of anti-MAP_5p and anti-MAP_2694295–303 antibodies were highly prevalent in patients with MS when compared to patients with NMOSD and controls. Several patients with MS had detectable anti-MAP_5p and anti-MAP_2694295–303 antibodies in the CSF. Furthermore, a group of patients with MS showed intrathecally restricted production of antibodies against these peptides. Women appeared to mount a stronger humoral response to mycobacterial peptides than men. No significant difference in the frequency of anti-MBP85–98 antibodies was found between patients with MS and those with NMOSD. These data highlight the zoonotic potential of MAP, which suggests its involvement in MS etiopathogenesis.

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Humoral response against host-mimetic homologous epitopes of Mycobacterium avium subsp. paratuberculosis in Japanese multiple sclerosis patients

Cited by 24 publications

References 30 publications

Systematic Assessment of Mycobacterium avium Subspecies Paratuberculosis Infections from 1911–2019: A Growth Analysis of Association with Human Autoimmune Diseases

Systematic Assessment of Mycobacterium avium Subspecies Paratuberculosis Infections from 1911–2019: A Growth Analysis of Association with Human Autoimmune Diseases

Presence Of Infection By Mycobacterium Avium Subsp. Paratuberculosis In The Blood Of Patients With Crohn’s Disease And Control Subjects Shown By Multiple Laboratory Culture And Antibody Methods

Anti-Mycobacterial Antibodies in Paired Cerebrospinal Fluid and Serum Samples from Japanese Patients with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder

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