eng URI http://hdl.handle.net/10795/3670 ιατρικές επιστήμες ασθένεια του νευρικού συστήματος κυτταρολογία The autoantibody to aquaporin-4 (AQP4) is a marker and a pathogenetic factor in Neuromyelitis Optica (NMO) (Devic’s syndrome). Our aim was to identify B-cell antigenic linear epitopes of the AQP4 protein and investigate similarities with other molecules. To this end, we screened sera from 21 patients positive for anti-AQP4 antibodies (study group), from 23 SLE and 23 pSS patients without neurologic involvement (disease controls) and from 28 healthy individuals (normal controls). Eleven peptides, spanning the entire intracellular and extracellular domains of the AQP4 molecule, were synthesized, and all sera were screened for anti-peptide antibodies by ELISA. Specificity was evaluated by homologous inhibition assays. NMO positive sera exhibited reactivity against 3 different peptides spanning the sequences aa1e22 (AQPpep1) (42.9% of patients), aa88e113 (AQPpep4) (33%) and aa252e275 (AQPpep8) (23.8%). All epitopes were localized in the intracellular domains of AQP4. Homologous inhibition rates were ranging from 71.1% to 84.3%. A 73% sequence homology was observed between AQPpep80 aa257e271, a 15-mer peptide part of the AQPpep8 aa252e275, and the aa219e233 domain of the Tax1-HTLV-1 binding protein (TAX1BP1), a host protein associated with replication of the Human T-Lymphotropic Virus 1 (HTLV-1). Antibodies against the AQP4 and the TAX1BP1 15-mer peptides were detected in 26.3% (N ¼ 5) and 31.6% (N ¼ 6) of NMO positive sera (rs ¼ 0.81, P < 0.0001). Healthy controls did not react with these peptides, while homologous and cross-inhibition assays confirmed binding specificity. This first epitope mapping for AQP4 reveals that a significant proportion of anti-AQP4 antibodies target linear epitopes localized in the intracellular domains of the channel. One of the epitopes displays high similarity with a portion of TAX1BP1 protein. 7 pp. LOMv1.0 creator LOMv1.0 publisher LOMv1.0 Scientific Coordinator LOMv1.0 Project Executing Organisation 2011-01-18 Digital Library of the Operational Programme "Education and Lifelong Learning" abstract types Text Central nervous system Systemic Lupus Erythematosus Autoimmune diseases Neuromyelitis optica Multiple sclerosis Epitope mapping Aquaporin-4 AQP4 Autoantibodies Molecular mimicry Κεντρικό νευρικό σύστημα Συστηματικός ερυθηματώδης λύκος Επιπολασμός Αντισώματα Οπτική νευρομυελίτιδα 1166443 application/pdf http://repository.edulll.gr/edulll/bitstream/10795/3670/2/3670_1.106_%ce%94%ce%97%ce%9c_18_1_11.pdf URI http://hdl.handle.net/10795/3670 LOMv1.0creator 2016-06-17T07:19:11Z LOMv1.0validator 2016-06-17T07:19:11Z LOMv1.0 gre no no Copyright EYD-EPEDBM (Operational Programme "Education and Lifelong Learning")