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Crohn’s patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes

About half of patients with Crohn’s disease (CD) develop selective serum IgG response to flagellin proteins of the Lachnospiraceae family. Here, we identified a dominant B cell peptide epitope in CD, locating in the highly conserved “hinge region” between the D0 and D1 domains at the amino-terminus...

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Autores principales: Zhao, Qing, Duck, Lennard Wayne, Killian, John T., Rosenberg, Alexander F., Mannon, Peter J., King, R. Glenn, Denson, Lee A., Kugathasan, Subra, Janoff, Edward N., Jenmalm, Maria C., Elson, Charles O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10441350/
https://www.ncbi.nlm.nih.gov/pubmed/37609309
http://dx.doi.org/10.1101/2023.08.08.552496
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author Zhao, Qing
Duck, Lennard Wayne
Killian, John T.
Rosenberg, Alexander F.
Mannon, Peter J.
King, R. Glenn
Denson, Lee A.
Kugathasan, Subra
Janoff, Edward N.
Jenmalm, Maria C.
Elson, Charles O.
author_facet Zhao, Qing
Duck, Lennard Wayne
Killian, John T.
Rosenberg, Alexander F.
Mannon, Peter J.
King, R. Glenn
Denson, Lee A.
Kugathasan, Subra
Janoff, Edward N.
Jenmalm, Maria C.
Elson, Charles O.
author_sort Zhao, Qing
collection PubMed
description About half of patients with Crohn’s disease (CD) develop selective serum IgG response to flagellin proteins of the Lachnospiraceae family. Here, we identified a dominant B cell peptide epitope in CD, locating in the highly conserved “hinge region” between the D0 and D1 domains at the amino-terminus of Lachnospiraceae flagellins. Serum IgG reactive to this epitope is present at an elevated level in adult CD patients and in pediatric CD patients at diagnosis. Most importantly, high levels of serum IgG to the hinge epitope were found in most infants from 3 different geographic regions (Uganda, Sweden, and the USA) at one year of age. This vigorous homeostatic response decrements with age as it is not present in healthy adults. These data identify a distinct subset of CD patients, united by a shared reactivity to this dominant flagellin epitope that may represent failure of a homeostatic response beginning in infancy.
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spelling pubmed-104413502023-08-22 Crohn’s patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes Zhao, Qing Duck, Lennard Wayne Killian, John T. Rosenberg, Alexander F. Mannon, Peter J. King, R. Glenn Denson, Lee A. Kugathasan, Subra Janoff, Edward N. Jenmalm, Maria C. Elson, Charles O. bioRxiv Article About half of patients with Crohn’s disease (CD) develop selective serum IgG response to flagellin proteins of the Lachnospiraceae family. Here, we identified a dominant B cell peptide epitope in CD, locating in the highly conserved “hinge region” between the D0 and D1 domains at the amino-terminus of Lachnospiraceae flagellins. Serum IgG reactive to this epitope is present at an elevated level in adult CD patients and in pediatric CD patients at diagnosis. Most importantly, high levels of serum IgG to the hinge epitope were found in most infants from 3 different geographic regions (Uganda, Sweden, and the USA) at one year of age. This vigorous homeostatic response decrements with age as it is not present in healthy adults. These data identify a distinct subset of CD patients, united by a shared reactivity to this dominant flagellin epitope that may represent failure of a homeostatic response beginning in infancy. Cold Spring Harbor Laboratory 2023-08-11 /pmc/articles/PMC10441350/ /pubmed/37609309 http://dx.doi.org/10.1101/2023.08.08.552496 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Zhao, Qing
Duck, Lennard Wayne
Killian, John T.
Rosenberg, Alexander F.
Mannon, Peter J.
King, R. Glenn
Denson, Lee A.
Kugathasan, Subra
Janoff, Edward N.
Jenmalm, Maria C.
Elson, Charles O.
Crohn’s patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes
title Crohn’s patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes
title_full Crohn’s patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes
title_fullStr Crohn’s patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes
title_full_unstemmed Crohn’s patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes
title_short Crohn’s patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes
title_sort crohn’s patients and healthy infants share immunodominant b cell response to commensal flagellin peptide epitopes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10441350/
https://www.ncbi.nlm.nih.gov/pubmed/37609309
http://dx.doi.org/10.1101/2023.08.08.552496
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