Rheumatoid arthritis sera antibodies to citrullinated collagen type II bind to joint cartilage

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Fältnamn	Indikatorer	Metadata
000		03235naa a2200409 4500
001		oai:prod.swepub.kib.ki.se:151232433
003		SwePub
008		240811s2022 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1512324332 URI
024	7	a https://doi.org/10.1186/s13075-022-02945-02 DOI
040		a (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Li, QX4 aut
245	1 0	a Rheumatoid arthritis sera antibodies to citrullinated collagen type II bind to joint cartilage
264		c 2022-11-22
264	1	b Springer Science and Business Media LLC,c 2022
520		a ObjectiveTo investigate the occurrence and frequency of anti-citrullinated protein antibodies (ACPA) to cyclic citrullinated type II collagen (COL2) epitope with a capacity to bind joint cartilage.MethodsLuminex immunoassay was used to analyze serum antibody reactivity to 10 COL2-citrullinated peptides (ACC10) and corresponding arginine peptide controls in rheumatoid arthritis (RA), osteoarthritis (OA), and healthy individuals’ cohorts. Top ten “promiscuous” sera (cross-reactive with all ACC10) and top ten “private” sera (restrictedly reactive with one ACC10 peptide) from RA and OA cohorts were selected. Enzyme-linked immunosorbent assay (ELISA) was used to detect response to native COL2. Sera were analyzed with naive and arthritic joints from DBA/1J mice by immunohistochemistry, using monoclonal ACPAs and COL2 reactive antibodies with human Fc as comparison. Staining specificity was confirmed with C1 (a major antibody epitope on COL2) mutated mice and competitive blocking with epitope-specific antibodies.ResultsAll patient sera bound ACC10 compared with control peptides but very few (3/40) bound native triple-helical COL2. Most sera (27/40) specifically bound to arthritic cartilage, whereas only one private RA serum bound to healthy cartilage. Despite very low titers, private sera from both RA and OA showed an epitope-specific response, documented by lack of binding to cartilage from C1-mutated mice and blocking binding to wild-type cartilage with a competitive monoclonal antibody. As a comparison, monoclonal ACPAs visualized typical promiscuous, or private reactivity to joint cartilage and other tissues.ConclusionACPA from RA and OA sera, reactive with citrullinated non-triple-helical COL2 peptides, can bind specifically to arthritic cartilage.
700	1	a Li, YP4 aut
700	1	a Liang, BB4 aut
700	1	a Xu, R4 aut
700	1	a Xu, BZ4 aut
700	1	a Lonnblom, Eu Karolinska Institutet4 aut
700	1	a Feng, H4 aut
700	1	a Bai, J4 aut
700	1	a Stawikowska, R4 aut
700	1	a Ge, CR4 aut
700	1	a Lu, AP4 aut
700	1	a Fields, GB4 aut
700	1	a Xiao, LB4 aut
700	1	a Holmdahl, Ru Karolinska Institutet4 aut
710	2	a Karolinska Institutet4 org
773	0	t Arthritis research & therapyd : Springer Science and Business Media LLCg 24:1, s. 257-q 24:1<257-x 1478-6362
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:151232433
856	4 8	u https://doi.org/10.1186/s13075-022-02945-0

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Av författaren/redakt...: Li, QX; Li, YP; Liang, BB; Xu, R; Xu, BZ; Lonnblom, E; visa fler...; Feng, H; Bai, J; Stawikowska, R; Ge, CR; Lu, AP; Fields, GB; Xiao, LB; Holmdahl, R; visa färre...

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Av lärosätet: Karolinska Institutet

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