Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782335906618802176 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4171545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT polymerosdimitrios bioinformaticandimmunologicalanalysisrevealslackofsupportformeaslesvirusrelatedmimicryincrohnsdisease AT tsiamouloszachariasp bioinformaticandimmunologicalanalysisrevealslackofsupportformeaslesvirusrelatedmimicryincrohnsdisease AT koutsoumpasandreasl bioinformaticandimmunologicalanalysisrevealslackofsupportformeaslesvirusrelatedmimicryincrohnsdisease AT smykdaniels bioinformaticandimmunologicalanalysisrevealslackofsupportformeaslesvirusrelatedmimicryincrohnsdisease AT mytilinaioumariag bioinformaticandimmunologicalanalysisrevealslackofsupportformeaslesvirusrelatedmimicryincrohnsdisease AT triantafylloukonstantinos bioinformaticandimmunologicalanalysisrevealslackofsupportformeaslesvirusrelatedmimicryincrohnsdisease AT bogdanosdimitriosp bioinformaticandimmunologicalanalysisrevealslackofsupportformeaslesvirusrelatedmimicryincrohnsdisease AT ladasspirosd bioinformaticandimmunologicalanalysisrevealslackofsupportformeaslesvirusrelatedmimicryincrohnsdisease |