Calreticulin binds preferentially with B cell linear epitopes of Ro60 kD autoantigen, enhancing recognition by anti-Ro60 kD autoantibodies

Staikou, EV; Routsias, JG; Makri, AA; Terzoglou, A; Sakarellos-Daitsiotis, M; Sakarellos, C; Panayotou, G; Moutsopoulos, HM; Tzioufas, AG

dc.contributor.author	Staikou, EV	en
dc.contributor.author	Routsias, JG	en
dc.contributor.author	Makri, AA	en
dc.contributor.author	Terzoglou, A	en
dc.contributor.author	Sakarellos-Daitsiotis, M	en
dc.contributor.author	Sakarellos, C	en
dc.contributor.author	Panayotou, G	en
dc.contributor.author	Moutsopoulos, HM	en
dc.contributor.author	Tzioufas, AG	en
dc.date.accessioned	2014-03-01T01:53:06Z
dc.date.available	2014-03-01T01:53:06Z
dc.date.issued	2003	en
dc.identifier.issn	0009-9104	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/26849
dc.subject	anti-Ro/SSA	en
dc.subject	B cell epitopes	en
dc.subject	calreticulin	en
dc.subject	Sjogren's syndrome	en
dc.subject	systemic lupus erythematosus	en
dc.subject.classification	Immunology	en
dc.subject.other	HEAT-SHOCK PROTEINS	en
dc.subject.other	ENDOPLASMIC-RETICULUM	en
dc.subject.other	AUTOIMMUNE-DISEASE	en
dc.subject.other	SYNTHETIC PEPTIDE	en
dc.subject.other	FINE SPECIFICITY	en
dc.subject.other	IN-VITRO	en
dc.subject.other	RIBONUCLEOPROTEIN	en
dc.subject.other	CHAPERONE	en
dc.subject.other	ANTIBODIES	en
dc.subject.other	CLASSIFICATION	en
dc.title	Calreticulin binds preferentially with B cell linear epitopes of Ro60 kD autoantigen, enhancing recognition by anti-Ro60 kD autoantibodies	en
heal.type	journalArticle	en
heal.language	English	en
heal.publicationDate	2003	en
heal.abstract	Calreticulin is a molecular chaperone to newly synthesized polypeptides. Previous studies suggested that calreticulin is probably a protein member of the Ro/La RNP complex. The aims of this study were (a) to investigate whether linear B cell epitopes of the Ro/La RNP complex are bound to calreticulin and (b) if the complex peptide-calreticulin is recognized specifically by anti-Ro autoantibodies. Calreticulin was isolated from either human or pig spleen using a multi-step purification method and found to interact preferentially with biotinylated peptides derived from the sequence of the Ro60 kD 175-184aa(10p) and 216-232aa(17p). The interaction of the peptide-calreticulin complex was favoured by the combination of heat treatment, divalent cations and ATP. La/SSB epitopes did not react with calreticulin. Peptides corresponding to La/SSB epitopes as well as the common epitope of Sm did not interact with calreticulin. Thirty-eight anti-Ro60 KD positive and 23 anti-Ro60 kD negative sera of patients with systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (pSS) were tested. All anti-Ro60 kD positive sera bound the complex calreticulin-17p, while 95% of the same sera had activity against the complex calreticulin -10p. Tested individually, calreticulin, pep10p and pep17p presented very low reactivity (8%, 11% and 29%, respectively) against anti-Ro60 kD positive sera. Anti-Ro60 KD negative sera did not exhibit significant reactivity either with calreticulin, 10rho and 17rho or with the complexes calreticulin -10p and calreticulin-17p (<5%). These results suggest that calreticulin can induce conformation-dependent recognition of the Ro60 kD epitopes, leading eventually to their recognition by autoantibodies. This is the first time that such a relationship is shown between a chaperone protein and fragments of an intracellular autoantigen. This work also provides insights into the understanding of mechanisms for autoantibody production. Furthermore, this association can be proved useful for the development of new sensitive assays for autoantibody detection.	en
heal.publisher	BLACKWELL PUBLISHING LTD	en
heal.journalName	CLINICAL AND EXPERIMENTAL IMMUNOLOGY	en
dc.identifier.isi	ISI:000185345200022	en
dc.identifier.volume	134	en
dc.identifier.issue	1	en
dc.identifier.spage	143	en
dc.identifier.epage	150	en