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Humoral immune response to citrullinated collagen type II determinants in early rheumatoid arthritis

Burkhardt, H ; Sehnert, B ; Bockermann, Robert LU ; Engstrom, A ; Kalden, JR and Holmdahl, Rikard LU (2005) In European Journal of Immunology 35(5). p.1643-1652
Abstract
Collagen type II (CII) is a relevant joint-specific autoantigen in the pathogenesis of rheumatoid arthritis (RA). Whereas the reasons for the breakage of self tolerance to this major cartilage component are still enigmatic, T cell responses to glycosylated CII determinants in RA patients indicate that post-translational modifications play a role. Since the conversion of arginine into citrulline by peptidylarginine deiminases (PAD) in some non-joint-specific antigens such as filaggrin or fibrin has been shown to give rise to RA-specific humoral immune responses, we investigated whether PAD modification of cartilage-specific CII might affect its recognition by circulating autoantibodies in early RA. In vitro treatment with purified PAD led... (More)
Collagen type II (CII) is a relevant joint-specific autoantigen in the pathogenesis of rheumatoid arthritis (RA). Whereas the reasons for the breakage of self tolerance to this major cartilage component are still enigmatic, T cell responses to glycosylated CII determinants in RA patients indicate that post-translational modifications play a role. Since the conversion of arginine into citrulline by peptidylarginine deiminases (PAD) in some non-joint-specific antigens such as filaggrin or fibrin has been shown to give rise to RA-specific humoral immune responses, we investigated whether PAD modification of cartilage-specific CII might affect its recognition by circulating autoantibodies in early RA. In vitro treatment with purified PAD led to arginine deimination of native CII or of synthetic CII peptides as evidenced by amino acid analysis. The citrullination resulted in modified recognition of the immunodominant CII epitope C1(III) (amino acid residues 359-369) by murine and human antibodies. In a cohort of early RA patients (n = 286), IgG antibodies directed toward a synthetic citrullinated C1(III) peptide (citC1(III)-P) were detectable with a prevalence of 40.4%. The partial autoantibody cross-reactivity between citC1(III)-P and citrullinated peptides mimicking epitopes of the cytoskeletal autoantigen filaggrin suggests that autoimmunity to cartilage-specific modified self might be a critical intermediate bridging recognition of PAD-modified extra-articular autoantigens with the disruption of tolerance to native cartilage constituents. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
rheumatoid arthritis, autoantibodies, collagen, citrullination
in
European Journal of Immunology
volume
35
issue
5
pages
1643 - 1652
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000229097100034
  • pmid:15832289
  • scopus:18844386764
ISSN
1521-4141
DOI
10.1002/eji.200526000
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
id
4ddd4acf-d421-43ff-93ce-dff788d67cdf (old id 240256)
date added to LUP
2016-04-01 12:27:58
date last changed
2022-03-29 01:13:38
@article{4ddd4acf-d421-43ff-93ce-dff788d67cdf,
  abstract     = {{Collagen type II (CII) is a relevant joint-specific autoantigen in the pathogenesis of rheumatoid arthritis (RA). Whereas the reasons for the breakage of self tolerance to this major cartilage component are still enigmatic, T cell responses to glycosylated CII determinants in RA patients indicate that post-translational modifications play a role. Since the conversion of arginine into citrulline by peptidylarginine deiminases (PAD) in some non-joint-specific antigens such as filaggrin or fibrin has been shown to give rise to RA-specific humoral immune responses, we investigated whether PAD modification of cartilage-specific CII might affect its recognition by circulating autoantibodies in early RA. In vitro treatment with purified PAD led to arginine deimination of native CII or of synthetic CII peptides as evidenced by amino acid analysis. The citrullination resulted in modified recognition of the immunodominant CII epitope C1(III) (amino acid residues 359-369) by murine and human antibodies. In a cohort of early RA patients (n = 286), IgG antibodies directed toward a synthetic citrullinated C1(III) peptide (citC1(III)-P) were detectable with a prevalence of 40.4%. The partial autoantibody cross-reactivity between citC1(III)-P and citrullinated peptides mimicking epitopes of the cytoskeletal autoantigen filaggrin suggests that autoimmunity to cartilage-specific modified self might be a critical intermediate bridging recognition of PAD-modified extra-articular autoantigens with the disruption of tolerance to native cartilage constituents.}},
  author       = {{Burkhardt, H and Sehnert, B and Bockermann, Robert and Engstrom, A and Kalden, JR and Holmdahl, Rikard}},
  issn         = {{1521-4141}},
  keywords     = {{rheumatoid arthritis; autoantibodies; collagen; citrullination}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1643--1652}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{European Journal of Immunology}},
  title        = {{Humoral immune response to citrullinated collagen type II determinants in early rheumatoid arthritis}},
  url          = {{http://dx.doi.org/10.1002/eji.200526000}},
  doi          = {{10.1002/eji.200526000}},
  volume       = {{35}},
  year         = {{2005}},
}