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Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn’s disease

BACKGROUND: A link between measles virus and Crohn’s disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry. METHODS: The BLAST2p program was used to identify amino acid sequence simila...

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Autores principales: Polymeros, Dimitrios, Tsiamoulos, Zacharias P, Koutsoumpas, Andreas L, Smyk, Daniel S, Mytilinaiou, Maria G, Triantafyllou, Konstantinos, Bogdanos, Dimitrios P, Ladas, Spiros D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171545/
https://www.ncbi.nlm.nih.gov/pubmed/25168804
http://dx.doi.org/10.1186/s12916-014-0139-9
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author Polymeros, Dimitrios
Tsiamoulos, Zacharias P
Koutsoumpas, Andreas L
Smyk, Daniel S
Mytilinaiou, Maria G
Triantafyllou, Konstantinos
Bogdanos, Dimitrios P
Ladas, Spiros D
author_facet Polymeros, Dimitrios
Tsiamoulos, Zacharias P
Koutsoumpas, Andreas L
Smyk, Daniel S
Mytilinaiou, Maria G
Triantafyllou, Konstantinos
Bogdanos, Dimitrios P
Ladas, Spiros D
author_sort Polymeros, Dimitrios
collection PubMed
description BACKGROUND: A link between measles virus and Crohn’s disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry. METHODS: The BLAST2p program was used to identify amino acid sequence similarities between five measles virus and 56 intestinal proteins. Antibody responses to measles/human mimics were tested by an in-house ELISA using serum samples from 50 patients with CD, 50 with ulcerative colitis (UC), and 38 matched healthy controls (HCs). RESULTS: We identified 15 sets of significant (>70%) local amino acid homologies from two measles antigens, hemagglutinin-neuraminidase and fusion-glycoprotein, and ten human intestinal proteins. Reactivity to at least one measles 15-meric mimicking peptide was present in 27 out of 50 (54%) of patients with CD, 24 out of 50 (48%) with UC (CD versus UC, p = 0.68), and 13 out of 38 (34.2%) HCs (CD versus HC, p = 0.08). Double reactivity to at least one measles/human pair was present in four out of 50 (8%) patients with CD, three out of 50 (6%) with UC (p = 0.99), and in three out of 38 (7.9%) HCs (p >0.05 for all). Titration experiments yielded different extinction curves for anti-measles and anti-human intestinal double-reactive antibodies. Epitope prediction algorithms and three-dimensional modeling provided bioinformatic confirmation for the observed antigenicity of the main measles virus epitopic regions. CONCLUSIONS: Measles sequences mimicking intestinal proteins are frequent targets of antibody responses in patients with CD, but this reactivity lacks disease specificity and does not initiate cross-reactive responses to intestinal mimics. We conclude that there is no involvement of measles/human molecular mimicry in the etiopathogenesis of CD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0139-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-41715452014-10-23 Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn’s disease Polymeros, Dimitrios Tsiamoulos, Zacharias P Koutsoumpas, Andreas L Smyk, Daniel S Mytilinaiou, Maria G Triantafyllou, Konstantinos Bogdanos, Dimitrios P Ladas, Spiros D BMC Med Research Article BACKGROUND: A link between measles virus and Crohn’s disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry. METHODS: The BLAST2p program was used to identify amino acid sequence similarities between five measles virus and 56 intestinal proteins. Antibody responses to measles/human mimics were tested by an in-house ELISA using serum samples from 50 patients with CD, 50 with ulcerative colitis (UC), and 38 matched healthy controls (HCs). RESULTS: We identified 15 sets of significant (>70%) local amino acid homologies from two measles antigens, hemagglutinin-neuraminidase and fusion-glycoprotein, and ten human intestinal proteins. Reactivity to at least one measles 15-meric mimicking peptide was present in 27 out of 50 (54%) of patients with CD, 24 out of 50 (48%) with UC (CD versus UC, p = 0.68), and 13 out of 38 (34.2%) HCs (CD versus HC, p = 0.08). Double reactivity to at least one measles/human pair was present in four out of 50 (8%) patients with CD, three out of 50 (6%) with UC (p = 0.99), and in three out of 38 (7.9%) HCs (p >0.05 for all). Titration experiments yielded different extinction curves for anti-measles and anti-human intestinal double-reactive antibodies. Epitope prediction algorithms and three-dimensional modeling provided bioinformatic confirmation for the observed antigenicity of the main measles virus epitopic regions. CONCLUSIONS: Measles sequences mimicking intestinal proteins are frequent targets of antibody responses in patients with CD, but this reactivity lacks disease specificity and does not initiate cross-reactive responses to intestinal mimics. We conclude that there is no involvement of measles/human molecular mimicry in the etiopathogenesis of CD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0139-9) contains supplementary material, which is available to authorized users. BioMed Central 2014-08-28 /pmc/articles/PMC4171545/ /pubmed/25168804 http://dx.doi.org/10.1186/s12916-014-0139-9 Text en © Polymeros et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Polymeros, Dimitrios
Tsiamoulos, Zacharias P
Koutsoumpas, Andreas L
Smyk, Daniel S
Mytilinaiou, Maria G
Triantafyllou, Konstantinos
Bogdanos, Dimitrios P
Ladas, Spiros D
Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn’s disease
title Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn’s disease
title_full Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn’s disease
title_fullStr Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn’s disease
title_full_unstemmed Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn’s disease
title_short Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn’s disease
title_sort bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in crohn’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171545/
https://www.ncbi.nlm.nih.gov/pubmed/25168804
http://dx.doi.org/10.1186/s12916-014-0139-9
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