Search: WFRF:(Toes Rene E. M.)
> (2015-2019) >
Structural Basis of...
Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies
-
- Ge, Changrong (author)
- Karolinska Institutet,Karolinska Inst, Sweden
-
- Xu, Bingze (author)
- Karolinska Institutet,Karolinska Inst, Sweden
-
- Liang, Bibo (author)
- Karolinska Inst, Stockholm, Sweden.;Southern Med Univ, Guangzhou, Guangdong, Peoples R China.
-
show more...
-
- Lonnblom, Erik (author)
- Karolinska Institutet,Karolinska Inst, Sweden
-
- Lundstrom, Susanna L. (author)
- Karolinska Institutet,Karolinska Inst, Sweden
-
- Zubarev, Roman A. (author)
- Karolinska Institutet,Karolinska Inst, Sweden
-
- Ayoglu, Burcu (author)
- KTH,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, Stockholm, Sweden
-
- Nilsson, Peter (author)
- KTH,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, Stockholm, Sweden
-
- Skogh, Thomas (author)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
-
- Kastbom, Alf (author)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
-
- Malmstrom, Vivianne (author)
- Karolinska Institutet,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
-
- Klareskog, Lars (author)
- Karolinska Institutet,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
-
- Toes, Rene E. M. (author)
- Leiden Univ, Med Ctr, Leiden, Netherlands.
-
- Rispens, Theo (author)
- Univ Amsterdam, Amsterdam, Netherlands.
-
- Dobritzsch, Doreen, 1972- (author)
- Uppsala universitet,Biokemi,Uppsala Univ, Sweden
-
- Holmdahl, Rikard (author)
- Karolinska Institutet,Karolinska Inst, Sweden; Southern Med Univ, Peoples R China
-
show less...
-
(creator_code:org_t)
- 2019-01-04
- 2019
- English.
-
In: Arthritis & Rheumatology. - : WILEY. - 2326-5191 .- 2326-5205. ; 71:2, s. 210-221
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
http://kipublication...
-
https://urn.kb.se/re...
-
show less...
Abstract
Subject headings
Close
- Objective Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. Methods Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. Results Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. Conclusion These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Ge, Changrong
-
Xu, Bingze
-
Liang, Bibo
-
Lonnblom, Erik
-
Lundstrom, Susan ...
-
Zubarev, Roman A ...
-
show more...
-
Ayoglu, Burcu
-
Nilsson, Peter
-
Skogh, Thomas
-
Kastbom, Alf
-
Malmstrom, Vivia ...
-
Klareskog, Lars
-
Toes, Rene E. M.
-
Rispens, Theo
-
Dobritzsch, Dore ...
-
Holmdahl, Rikard
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Immunology in th ...
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Rheumatology and ...
- Articles in the publication
-
Arthritis & Rheu ...
- By the university
-
Royal Institute of Technology
-
Uppsala University
-
Karolinska Institutet
-
Linköping University