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FältnamnIndikatorerMetadata
00005947naa a2200625 4500
001oai:DiVA.org:kth-244541
003SwePub
008190412s2019 | |||||||||||000 ||eng|
009oai:DiVA.org:uu-377677
009oai:prod.swepub.kib.ki.se:140183895
009oai:DiVA.org:liu-154566
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-2445412 URI
0247 a https://doi.org/10.1002/art.406982 DOI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3776772 URI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1401838952 URI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1545662 URI
040 a (SwePub)kthd (SwePub)uud (SwePub)kid (SwePub)liu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Ge, Changrongu Karolinska Institutet,Karolinska Inst, Sweden4 aut
2451 0a Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies
264 c 2019-01-04
264 1b WILEY,c 2019
338 a print2 rdacarrier
500 a QC 20190412
500 a Funding Agencies|Swedish Strategic Science Foundation; Knut and Alice Wallenberg Foundation; Swedish Research Council; Guangdong province [201001Y04675344]; EU Innovative Medicine Initiative (BeTheCure grant); European Community Seventh Framework Programme (FP7/2007-2013) under BioStruct-X [283570]
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the medical area0 (SwePub)301102 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Reumatologi och inflammation0 (SwePub)302102 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Rheumatology and Autoimmunity0 (SwePub)302102 hsv//eng
7001 a Xu, Bingzeu Karolinska Institutet,Karolinska Inst, Sweden4 aut
7001 a Liang, Bibou Karolinska Inst, Stockholm, Sweden.;Southern Med Univ, Guangzhou, Guangdong, Peoples R China.4 aut
7001 a Lonnblom, Eriku Karolinska Institutet,Karolinska Inst, Sweden4 aut
7001 a Lundstrom, Susanna L.u Karolinska Institutet,Karolinska Inst, Sweden4 aut
7001 a Zubarev, Roman A.u Karolinska Institutet,Karolinska Inst, Sweden4 aut
7001 a Ayoglu, Burcuu KTH,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, Stockholm, Sweden4 aut0 (Swepub:kth)u1kfjubd
7001 a Nilsson, Peteru KTH,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, Stockholm, Sweden4 aut0 (Swepub:kth)u1ws88sk
7001 a Skogh, Thomasu Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland4 aut0 (Swepub:liu)thosk00
7001 a Kastbom, Alfu Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland4 aut0 (Swepub:liu)alfka05
7001 a Malmstrom, Vivianneu Karolinska Institutet,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden4 aut
7001 a Klareskog, Larsu Karolinska Institutet,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden4 aut
7001 a Toes, Rene E. M.u Leiden Univ, Med Ctr, Leiden, Netherlands.4 aut
7001 a Rispens, Theou Univ Amsterdam, Amsterdam, Netherlands.4 aut
7001 a Dobritzsch, Doreen,d 1972-u Uppsala universitet,Biokemi,Uppsala Univ, Sweden4 aut0 (Swepub:uu)dordo526
7001 a Holmdahl, Rikardu Karolinska Institutet,Karolinska Inst, Sweden; Southern Med Univ, Peoples R China4 aut
7102 a Karolinska Institutetb Karolinska Inst, Sweden4 org
7730 t Arthritis & Rheumatologyd : WILEYg 71:2, s. 210-221q 71:2<210-221x 2326-5191x 2326-5205
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-244541
8564 8u https://doi.org/10.1002/art.40698
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-377677
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:140183895
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-154566

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