Antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.

<h4>Objective</h4>The immune response to post-translationally modified antigens is a key characteristic of rheumatoid arthritis. Carbamylation is such a posttranslational modification. Recently, we demonstrated that autoantibodies recognizing carbamylated proteins are present in sera of...

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Autores principales:	Jeroen N Stoop, Bi-Sheng Liu, Jing Shi, Diahann T S L Jansen, Martin Hegen, Tom W J Huizinga, Leendert A Trouw, René E M Toes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b59842cee0e94863a8b2d99c5ea59403
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spelling	oai:doaj.org-article:b59842cee0e94863a8b2d99c5ea594032021-11-25T06:08:23ZAntibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.1932-620310.1371/journal.pone.0102163https://doaj.org/article/b59842cee0e94863a8b2d99c5ea594032014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25025869/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>The immune response to post-translationally modified antigens is a key characteristic of rheumatoid arthritis. Carbamylation is such a posttranslational modification. Recently, we demonstrated that autoantibodies recognizing carbamylated proteins are present in sera of rheumatoid arthritis. The molecular mechanisms underlying the break of tolerance and hence the induction of anti-CarP antibody responses are unknown as well as their appearance in mouse models for systemic arthritis. Therefore we analyzed their appearance in the mouse collagen-induced arthritis model.<h4>Methods</h4>collagen induced arthritis was induced by immunization with type II collagen in complete Freund's adjuvant. Arthritis severity was monitored by clinical scoring and anti-CarP antibody levels were determined by ELISA.<h4>Results</h4>Anti-CarP antibodies were detectable in mice with collagen induced arthritis. We did not detect ACPA in mice with collagen induced arthritis. The specificity of the antibodies for carbamylated proteins was confirmed by inhibition assays and immunoblotting. Injection with complete Freund's adjuvant without type II collagen could also induce anti-CarP antibodies, however, in mice with arthritis, the anti-CarP antibody response was stronger and developed more rapidly. The onset of collagen induced arthritis was preceded by an increase of anti-CarP IgG2a levels in the serum.<h4>Conclusion</h4>In mice with collagen induced arthritis we did not observe an immune response against citrullinated antigens, but we did observe an immune response against carbamylated antigens. This anti-CarP response already appeared before disease onset, indicating that collagen induced arthritis can be used as an in vivo model to study anti-CarP antibodies. Our data also indicate that the tolerance to carbamylated proteins, in contrast to the response to citrullinated proteins, is easily broken and that arthritis boosts the immune response against these proteins. The anti-CarP response in mice with CIA can be used as a model for immune responses to post-translationally modified proteins.Jeroen N StoopBi-Sheng LiuJing ShiDiahann T S L JansenMartin HegenTom W J HuizingaLeendert A TrouwRené E M ToesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e102163 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeroen N Stoop Bi-Sheng Liu Jing Shi Diahann T S L Jansen Martin Hegen Tom W J Huizinga Leendert A Trouw René E M Toes Antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.
description	<h4>Objective</h4>The immune response to post-translationally modified antigens is a key characteristic of rheumatoid arthritis. Carbamylation is such a posttranslational modification. Recently, we demonstrated that autoantibodies recognizing carbamylated proteins are present in sera of rheumatoid arthritis. The molecular mechanisms underlying the break of tolerance and hence the induction of anti-CarP antibody responses are unknown as well as their appearance in mouse models for systemic arthritis. Therefore we analyzed their appearance in the mouse collagen-induced arthritis model.<h4>Methods</h4>collagen induced arthritis was induced by immunization with type II collagen in complete Freund's adjuvant. Arthritis severity was monitored by clinical scoring and anti-CarP antibody levels were determined by ELISA.<h4>Results</h4>Anti-CarP antibodies were detectable in mice with collagen induced arthritis. We did not detect ACPA in mice with collagen induced arthritis. The specificity of the antibodies for carbamylated proteins was confirmed by inhibition assays and immunoblotting. Injection with complete Freund's adjuvant without type II collagen could also induce anti-CarP antibodies, however, in mice with arthritis, the anti-CarP antibody response was stronger and developed more rapidly. The onset of collagen induced arthritis was preceded by an increase of anti-CarP IgG2a levels in the serum.<h4>Conclusion</h4>In mice with collagen induced arthritis we did not observe an immune response against citrullinated antigens, but we did observe an immune response against carbamylated antigens. This anti-CarP response already appeared before disease onset, indicating that collagen induced arthritis can be used as an in vivo model to study anti-CarP antibodies. Our data also indicate that the tolerance to carbamylated proteins, in contrast to the response to citrullinated proteins, is easily broken and that arthritis boosts the immune response against these proteins. The anti-CarP response in mice with CIA can be used as a model for immune responses to post-translationally modified proteins.
format	article
author	Jeroen N Stoop Bi-Sheng Liu Jing Shi Diahann T S L Jansen Martin Hegen Tom W J Huizinga Leendert A Trouw René E M Toes
author_facet	Jeroen N Stoop Bi-Sheng Liu Jing Shi Diahann T S L Jansen Martin Hegen Tom W J Huizinga Leendert A Trouw René E M Toes
author_sort	Jeroen N Stoop
title	Antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.
title_short	Antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.
title_full	Antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.
title_fullStr	Antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.
title_full_unstemmed	Antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.
title_sort	antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b59842cee0e94863a8b2d99c5ea59403
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Antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis.

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