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鉴定出两个高度抗原性的表位标记物，可预测视神经炎患者的多发性硬化症。

Identification of two highly antigenic epitope markers predicting multiple sclerosis in optic neuritis patients.

机构信息

Protobios Llc, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia.

Protobios Llc, Mäealuse 4, Tallinn 12618, Estonia.

出版信息

EBioMedicine. 2021 Feb;64:103211. doi: 10.1016/j.ebiom.2021.103211. Epub 2021 Jan 23.

DOI:10.1016/j.ebiom.2021.103211
PMID:33493797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7841498/
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.

摘要

背景

视神经炎 (ON) 可作为孤立发作出现，也可发展为多发性硬化症 (MS) 这一慢性自身免疫性疾病。哪些因素预示着 ON 向 MS 的进展仍知之甚少。

方法

我们使用模拟表位变异分析 (MVA) 对三个独立的临床队列（发现队列 (n=62)、验证队列 (n=20) 和外部队列 (n=421)）中的抗体表位谱进行了特征描述，MVA 是一种下一代噬菌体展示技术，用于鉴定与 ON 预后相关的表位。

结果

我们观察到 ON、MS 和对照组之间存在独特的表位谱，而血清和脑脊液的表位谱则高度相似。在进展为 MS 的 ON 患者中，检测到两个独特且高度免疫原性的表位 A 和 B。这些表位 A 和 B 与疱疹病毒抗原（EBV 的 VCA p18；CMV 的 gB）强烈相关。基于两个表位生物标志物分析，ROC 正确识别了 75%的 ON 发病 MS 患者（敏感性为 75%，特异性为 74.22%）。

结论

这是第一项使用 MVA 进行 MS 表位诊断的报告，该方法采用了无偏策略，用于鉴定疾病的新型免疫特征。

资金来源

爱沙尼亚教育、研究理事会（PRG573、PRG805 和 PSG691）、H2020-MSCA-RISE-2016（SZTEST）、H2020-NMBP-2017（PANBIORA）、赫尔辛基大学医院、玛丽和乔治·克恩罗特基金会、芬兰眼、西格丽德·尤塞利乌斯和马格努斯·埃克诺特基金会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe89/7841498/9374d9a3e362/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe89/7841498/3ea77a7e99a3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe89/7841498/b97a2f5b8208/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe89/7841498/3f6659ee88a3/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe89/7841498/9374d9a3e362/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe89/7841498/3ea77a7e99a3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe89/7841498/b97a2f5b8208/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe89/7841498/3f6659ee88a3/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe89/7841498/9374d9a3e362/gr4.jpg

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