Identification of two highly antigenic epitope markers predicting multiple sclerosis in optic neuritis patients
Helle Sadam,
Arno Pihlak,
Mariliis Jaago,
Nadežda Pupina,
Annika Rähni,
Maarja Toots,
Antti Vaheri,
Janne K. Nieminen,
Mika Siuko,
Pentti J. Tienari,
Kaia Palm
Affiliations
Helle Sadam
Protobios Llc, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia
Arno Pihlak
Protobios Llc, Mäealuse 4, Tallinn 12618, Estonia
Mariliis Jaago
Protobios Llc, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia
Nadežda Pupina
Protobios Llc, Mäealuse 4, Tallinn 12618, Estonia
Annika Rähni
Protobios Llc, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia
Maarja Toots
Protobios Llc, Mäealuse 4, Tallinn 12618, Estonia
Antti Vaheri
Department of Virology, University of Helsinki, Medicum, Haartmaninkatu 3, 00014, Finland
Janne K. Nieminen
Neurology, Neurocentre, Helsinki University Hospital and Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, Helsinki 00014 Finland
Mika Siuko
Department of Ophthalmology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
Pentti J. Tienari
Neurology, Neurocentre, Helsinki University Hospital and Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, Helsinki 00014 Finland
Kaia Palm
Protobios Llc, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia; Corresponding author.
Background: Optic neuritis (ON) can occur as an isolated episode or will develop to multiple sclerosis (MS) a chronic autoimmune disease. What predicts ON progression to MS remains poorly understood. Methods: We characterised the antibody epitope repertoire in three independent clinical cohorts (discovery (n = 62), validation (n = 20) and external cohort (n = 421)) using mimotope variation analysis (MVA), a next generation phage display technology to identify epitopes that associate with prognosis of ON. Findings: We observed distinct epitope profiles for ON, MS and the controls, whereas epitope repertoires of sera and CSF were highly similar. Two unique and highly immunogenic epitopes A and B were detected in subjects with ON progressing to MS. These epitopes A and B were strongly associated with herpesviral antigens (VCA p18 of Epstein-Barr virus (EBV); gB of Cytomegalovirus (CMV)). ROC addressed 75% of MS subjects with ON onset correctly (at 75% sensitivity and 74.22% specificity) based on the two-epitope biomarker analysis. Interpretation: This is the first report on epitope diagnostics for MS employing the unbiased strategy of MVA for identification of novel immunological features of disease. Funding: The Estonian Ministry of Education, The Estonian Research Council (PRG573, PRG805 and PSG691), H2020-MSCA-RISE-2016 (SZTEST), H2020-NMBP-2017 (PANBIORA), Helsinki University Hospital, Mary and Georg C. Ehrnrooth, Finnish Eye, Sigrid Jusélius and Magnus Ehrnrooth Foundations.
