Serum proteome characterizes sequence of CNS injury in pre-symptomatic multiple sclerosis

The timing of the biological onset of multiple sclerosis (MS) is unclear. We utilized high-throughput discovery proteomics and samples from pre-symptomatic individuals with MS (pwMS) and matched healthy controls (HC) to define the biological neurological onset and characterize involved mechanisms. Remarkably, myelin injury was seen 7-8 years before the symptomatic onset and preceded evidence of axonal injury by 1-2 years. By contrast, astrocyte involvement became evident only at clinical onset. Numerous changes in the serum proteome indicate the involvement of interleukin 3 and nuclear factor kappa B pathways during the pre-symptomatic stage. A protein biomarker panel identified pre-symptomatic pwMS from HC with 95% sensitivity. Additionally, pwMS with a distinct autoantibody signature showed increased immune cell activity compared to those without. Our findings can help decipher the pathophysiology of MS as well as the cascade of CNS injury and facilitate early detection of MS in high-..., , , # Data from: Serum proteome characterizes sequence of CNS injury in pre-symptomatic multiple sclerosis

[https://doi.org/10.5061/dryad.fttdz093t](https://doi.org/10.5061/dryad.fttdz093t)

## Description of the data and file structure

Proteomic data were generated from serum collected from selected participants of the Department of Defense Serum Repository. Participants included people who developed multiple sclerosis and matched healthy controls. Data generated on the Olink platform using the Olink Explore HT kit. For an in-depth description of the participant selection and data processing, see the related manuscript.

### Files and variables

#### File: dodsr.ms.proteomics.csv

**Description:** .csv file containing basic demographics and clinical data, as well as Olink measurements from all included participants from the Department of Defense Serum Repository

##### Variables

* StudyID: anonymized participant ID
* timepoint: time point in relation to symptomatic multiple sclerosis on..., All participant IDs, datasets, and samples were fully anonymized by the Department of Defense Serum Repository (DODSR) staff prior to being provided for this research. As a result, the dataset received and subsequently uploaded contains no personally identifiable information (PII).

This study was reviewed and approved by both the Office of Human Research Oversight (OHRO), U.S. Army Medical Research and Development Command (USAMRDC), and the University of California, San Francisco (UCSF) Institutional Review Board (IRB).