B-Cell epitope mapping of DNA topoisomerase I defines epitopes strongly associated with pulmonary fibrosis in systemic sclerosis

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dc.contributor.authorRizou, C.en
dc.contributor.authorIoannidis, J. P.en
dc.contributor.authorPanou-Pomonis, E.en
dc.contributor.authorSakarellos-Daitsiotis, M.en
dc.contributor.authorSakarellos, C.en
dc.contributor.authorMoutsopoulos, H. M.en
dc.contributor.authorVlachoyiannopoulos, P. G.en
dc.date.accessioned2015-11-24T19:33:24Z
dc.date.available2015-11-24T19:33:24Z
dc.identifier.issn1044-1549-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/23533
dc.rightsDefault Licence-
dc.subjectAmino Acid Sequenceen
dc.subjectAntibodies/pharmacologyen
dc.subjectB-Lymphocytes/enzymology/*immunologyen
dc.subjectBinding, Competitive/immunologyen
dc.subjectDNA Topoisomerases, Type I/chemistry/*immunologyen
dc.subjectEnzyme-Linked Immunosorbent Assayen
dc.subjectEpitope Mapping/*statistics & numerical dataen
dc.subjectEpitopesen
dc.subjectHeLa Cellsen
dc.subjectHumansen
dc.subjectMolecular Sequence Dataen
dc.subjectPeptide Fragments/chemistry/immunologyen
dc.subjectPredictive Value of Testsen
dc.subjectProportional Hazards Modelsen
dc.subjectProtein Structure, Tertiaryen
dc.subjectPulmonary Fibrosis/*immunology/pathologyen
dc.subjectScleroderma, Systemic/*immunology/pathologyen
dc.titleB-Cell epitope mapping of DNA topoisomerase I defines epitopes strongly associated with pulmonary fibrosis in systemic sclerosisen
heal.abstractWe hypothesized that B-cell epitope mapping of DNA Topoisomerase I (type-I topoisomerase, or Topo I) may define epitopes strongly associated with pulmonary interstitial fibrosis (PIF) in systemic sclerosis (SSc). B-cell epitope mapping of Topo I was performed using 63 20-mer peptides overlapping by eight residues and spanning the entire length of the Topo I sequence. These peptides, coupled to polystyrene pins, were tested for antibody binding by enzyme-linked immunosorbent assays (ELISAs) using immunoglobulin G fractions from anti-Topo I, anticentromere, anti-U3RNP-positive, and normal sera. Four major epitopes were recognized by anti-Topo I sera, but not from the control sera: WWEEERYPEGIKWKFLEHKG (205-224, epitope I), RIANFKIEPPGLFRGRGNHP (349-368, epitope II), PGHKWKEVRHDNKVTWLVSW (397-416, epitope III), and ELDGQEYVVEFDFLGKDSIR (517-536, epitope IV). Peptide-epitopes were then synthesized in their soluble forms and ELISA systems were developed. Epitopes II to IV are localized at highly exposed sites of the Topo I tertiary structure, whereas epitope I is localized at a less accessible site. In a cohort of 81 patients with SSc with clinical data on the evolution of their disease, patients with antibodies in their sera recognizing at least three of the four epitopes had 3.1 times (P = 0.02) the hazard of developing PIF compared with patients whose sera recognized no epitopes or only one or two of the four epitopes. The discrimination was much stronger than that achieved by the simple determination of Topo I antibodies by counterimmunoelectrophoresis and immunoblot (hazard ratio 1.7, P = 0.30) in the same patients. B-cell epitope mapping of the anti-Topo I response has identified four major epitopes which cumulatively show a strong association with the development of PIF in SSc.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/10696071-
heal.identifier.secondaryhttp://ajrcmb.atsjournals.org/content/22/3/344.full.pdf-
heal.journalNameAm J Respir Cell Mol Biolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2000-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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