Fine specificity of antibodies against AQP4: Epitope mapping reveals intracellular epitopes

Abstract 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 2...

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Bibliographic Details
Published in:Journal of autoimmunity 2011-05, Vol.36 (3), p.221-227
Main Authors: Kampylafka, E.I, Routsias, J.G, Alexopoulos, H, Dalakas, M.C, Moutsopoulos, H.M, Tzioufas, A.G
Format: Article
Language:English
Subjects:
Allergy and Immunology
Amino Acid Sequence
Aquaporin 4 - immunology
Autoantibodies
Autoantibodies - immunology
Epitope Mapping
Human T-lymphotropic virus 1
Humans
Immunodominant Epitopes - chemistry
Intracellular Signaling Peptides and Proteins - immunology
Molecular mimicry
Molecular Sequence Data
Neoplasm Proteins - immunology
Neuromyelitis optica
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Summary:Abstract 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 aa1–22 (AQPpep1) (42.9% of patients), aa88–113 (AQPpep4) (33%) and aa252–275 (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 AQPpep8′ aa257–271, a 15-mer peptide part of the AQPpep8 aa252–275, and the aa219–233 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  = 5) and 31.6% ( N  = 6) of NMO positive sera ( rs  = 0.81, P  
ISSN:0896-8411
1095-9157
DOI:10.1016/j.jaut.2011.01.004