EBioMedicine · 2021
Identification of two highly antigenic epitope markers predicting multiple sclerosis in optic neuritis patients.
СтатьяНазвание и аннотация: Перевод в очереди
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Sadam Helle, Pihlak Arno, Jaago Mariliis, Pupina Nadežda, Rähni Annika, Toots Maarja, Vaheri Antti, Nieminen Janne K, Siuko Mika, Tienari Pentti J, Palm Kaia
Аннотация
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.
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.