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      Mycobacterium avium subspecies Paratuberculosis and Crohn's Regional Ileitis: How Strong is Association?

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          Abstract

          Mycobacterium avium subsp. paratuberculosis (MAP) is a well-established etiological agent of Johne's disease in animals. In humans, similar clinical condition, first described by Crohn as regional ileitis in 1932, now known as Crohn's diseases (CD), has also been associated with this mycobacterial species. However, there are two schools of thoughts, one favoring MAP as its etiological agent while the second considers it as an immune-inflammatory condition triggered by an external factor. Onset of CD requires a series of events including predisposition of certain inherited genetic traits, associated environmental stimuli, and immune-inflammatory response. A combination of these factors probably leads to this disease. Recently, some human genes have also been identified which regulate ability to respond appropriately to the external factors. Added to these factors are concerns about the selection of clinical specimens and poor adherence to laboratory quality controls. The literature is full of contradictory findings, but there a lack of uniformity in the materials and methods used by many of these researchers. In this review, we provide our perspective under above circumstances and give our point of view which may open a platform for debate regarding the MAP as the etiological agent of human CD.

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          Most cited references48

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          Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.

          Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.
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            World Health Organization.

            Ala Alwan (2007)
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              Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn's disease.

              Crohn's disease, a form of inflammatory bowel disease, resembles some aspects of tuberculosis, leprosy, and paratuberculosis. The role of Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease is controversial. We tested for MAP by PCR and culture in buffy coat preparations from 28 individuals with Crohn's disease, nine with ulcerative colitis, and 15 without inflammatory bowel disease. MAP DNA in uncultured buffy coats was identified by PCR in 13 (46%) individuals with Crohn's disease, four (45%) with ulcerative colitis, and three (20%) without inflammatory bowel disease. Viable MAP was cultured from the blood of 14 (50%) patients with Crohn's disease, two (22%) with ulcerative colitis, and none of the individuals without inflammatory bowel disease. Current use of immunosuppressive medication did not correlate with a positive MAP culture. Sequencing of PCR products from MAP cultures confirmed the presence of the MAP-specific IS900 fragment. Among 11 MAP isolates assessed, we identified nine strains that were not identical. We detected viable MAP in peripheral blood in a higher proportion of individuals with Crohn's disease than in controls. These data contribute to the evidence that MAP might be a cause of Crohn's disease.
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                Author and article information

                Journal
                J Lab Physicians
                JLP
                Journal of Laboratory Physicians
                Medknow Publications & Media Pvt Ltd (India )
                0974-2727
                0974-7826
                Jul-Dec 2011
                : 3
                : 2
                : 69-74
                Affiliations
                [1]Department of Laboratory Medicine, Division of Clinical Microbiology, All India Institute of Medical Sciences, New Delhi, India
                [1 ]MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, University of the Witwatersrand and the National Health Laboratory Service, Johannesburg, South Africa
                Author notes
                Address for correspondence: Prof. Sarman Singh, E-mail: sarman_singh@ 123456yahoo.com
                Article
                JLP-3-69
                10.4103/0974-2727.86836
                3249720
                22219557
                f83542e4-5c1b-4a63-b845-6ec4349dc175
                Copyright: © Journal of Laboratory Physicians

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Review Article

                Clinical chemistry
                mycobacterium,crohn's disease,is900,johne's disease,mycobacterium avium subsp. paratuberculosis,paratuberculosis

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