Unmasking the anti-La/SSB response in sera from patients with Sjogren's syndrome by specific blocking of anti-idiotypic antibodies to La/SSB antigenic determinants

Routsias, JG; Touloupi, E; Dotsika, E; Moulia, A; Tsikaris, V; Sakarellos, C; Sakarellos-Daitsiotis, M; Moutsopoulos, HM; Tzioufas, AG

dc.contributor.author	Routsias, JG	en
dc.contributor.author	Touloupi, E	en
dc.contributor.author	Dotsika, E	en
dc.contributor.author	Moulia, A	en
dc.contributor.author	Tsikaris, V	en
dc.contributor.author	Sakarellos, C	en
dc.contributor.author	Sakarellos-Daitsiotis, M	en
dc.contributor.author	Moutsopoulos, HM	en
dc.contributor.author	Tzioufas, AG	en
dc.date.accessioned	2014-03-01T01:52:14Z
dc.date.available	2014-03-01T01:52:14Z
dc.date.issued	2002	en
dc.identifier.issn	1076-1551	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/26606
dc.subject.classification	Biochemistry & Molecular Biology	en
dc.subject.classification	Cell Biology	en
dc.subject.classification	Medicine, Research & Experimental	en
dc.subject.other	T-CELL DETERMINANTS	en
dc.subject.other	LINKED-IMMUNOSORBENT-ASSAY	en
dc.subject.other	LA SS-B	en
dc.subject.other	COMPLEMENTARY PEPTIDE	en
dc.subject.other	F(AB')2 FRAGMENTS	en
dc.subject.other	GENETIC-CODE	en
dc.subject.other	AUTOANTIBODIES	en
dc.subject.other	AUTOANTIGEN	en
dc.subject.other	RECOGNITION	en
dc.subject.other	PROTEIN	en
dc.title	Unmasking the anti-La/SSB response in sera from patients with Sjogren's syndrome by specific blocking of anti-idiotypic antibodies to La/SSB antigenic determinants	en
heal.type	journalArticle	en
heal.language	English	en
heal.publicationDate	2002	en
heal.abstract	Background: Autoantigen La/SSB is molecular target of humoral autoimmunity in patients with primary Sjogren's Syndrome (pSS) and systemic lupus erythematosus (SLE). in this study, we investigated the existence and possible influence of anti-idiotypic response to anti-La/SSB antibodies. Materials and Methods: Synthetic peptide analogs (pep) of the major antigenic determinants of La/SSB (289-308aa and 349-364aa) were prepared. Based on "molecular recognition" theory, complementary peptides (cpep), derived by anti-parallel readings of the noncoding strand of La/SSB DNA encoding for its antigenic determinants, were constructed. Sera from 150 patients with anti-La/SSB antibodies, 30 patients without anti-La/SSB antibodies, and 42 normal individuals were tested against all four peptides. F(ab')(2) fragments from anti-peptide IgG were prepared and F(ab')(2) - IgG interactions were evaluated using a specific anti-idiotypic ELISA. Results: All four peptides were recognized by anti-La positive sera (83% and 51% for pep and cpep 349-364 and 51% and 28% for pep and cpep289-308, respectively). Anti-cpep F(ab')(2) bound to a common idiotype (Id) located within or spatially close to the antigen combining site of anti La/SSB (anti-pep) antibodies. Homologous and cross-inhibition experiments further confirmed this relation. The anti-idiotypic antibodies inhibited the anti-La/SSB antibody binding to recombinant La/SSB by 91%. To overcome the anti-idiotypic interference in anti-La/SSB detection, a specific assay was developed. Sera were heated for dissociation of Id-anti-Id complexes, anti-Id antibodies blocked with cpep, and anti-La/SSB reactivity was recovered. Application of this method to anti-Ro positive-anti-La/SSB "negative" sera showed that all anti-Ro/SSA positive autoimmune sera also possess anti-La/SSB antibodies. This reaction was not observed in 14 anti-Ro negative- anti-Sm/RNP positive sera from patients with SLE. Conclusions: Autoimmune sera from patients with pSS and SLE contain anti-idiotypic antibodies targeting a common anti-La/SSB idiotype. These antibodies can be detected using complementary peptides of La/SSB epitopes. The antiidiotypic antibodies mask the anti-La/SSB response. Hidden anti-La/SSB antibodies can be released and detected using complementary epitope analogs.	en
heal.publisher	JOHNS HOPKINS UNIV PRESS	en
heal.journalName	MOLECULAR MEDICINE	en
dc.identifier.isi	ISI:000178088000001	en
dc.identifier.volume	8	en
dc.identifier.issue	6	en
dc.identifier.spage	A3	en
dc.identifier.epage	303	en