Ontology highlight
ABSTRACT: 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.
SUBMITTER: Sadam H
PROVIDER: S-EPMC7841498 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Sadam Helle H Pihlak Arno A Jaago Mariliis M Pupina Nadežda N Rähni Annika A Toots Maarja M Vaheri Antti A Nieminen Janne K JK Siuko Mika M Tienari Pentti J PJ Palm Kaia K
EBioMedicine 20210123
<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]