# Retrospective In Silico Analysis of Routine Laboratory Data Supports a Specific Association of Epstein–Barr Virus and Multiple Sclerosis

## TL;DR

A study of lab data shows that Epstein–Barr virus is strongly linked to multiple sclerosis compared to other diseases, suggesting EBV could be a key factor in MS.

## Contribution

The study provides strong evidence for a specific association between EBV and MS using real-world laboratory data.

## Key findings

- All correctly diagnosed MS patients were EBV seropositive, while other diseases showed lower EBV seroprevalence.
- MS patients had higher Epstein–Barr nuclear antigen-1 antibodies compared to other diseases.
- Intrathecal antibody production to EBV was less frequent in MS than to other common viruses.

## Abstract

We conducted a retrospective in silico analysis of routine laboratory data (RISAROLDA) to study the association of Epstein–Barr virus (EBV) and multiple sclerosis (MS).

Patients with MS and 10 different inflammatory/neoplastic diseases were identified by ICD10 codes. Results of routine laboratory testing for antibodies to EBV, measles, mumps, rubella, herpes simplex virus, varicella zoster virus and cytomegalovirus were extracted using a digital tool.

Among 10,669 patients with MS and 42,222 controls, EBV serologies were available from 492 (4.6%) patients with MS and 1918 (4.5%) controls. While all but three patients with an ICD10 diagnosis of MS were EBV seropositive, closer inspection of the three EBV seronegative patients revealed they were misdiagnosed with MS, resulting in a 100% EBV seroprevalence in the remaining 489 patients with MS. In contrast, EBV seroprevalences were lower in all other diseases (78.6%–97.8%). Serum antibodies to the Epstein–Barr nuclear antigen‐1, but not to the viral capsid antigen, were higher in patients with MS than in all other diseases. In patients with MS, seroprevalences of all other common viruses were lower than those of EBV, but the frequency of intrathecal production of antibodies to EBV was lower than that of other common viruses.

These findings suggest that the association of EBV and MS is specific for MS as compared to various other inflammatory/neoplastic diseases and that a negative EBV serology might be a marker for the absence of MS. RISAROLDA is a powerful approach for the screening of real‐world laboratory data.

To study the association of Epstein–Barr virus (EBV) and multiple sclerosis (MS) as compared to 10 different control diseases, 10,669 patients with MS and 42,222 controls were identified by ICD10 codes and their available antiviral serologies retrieved from the hospital information system. EBV seroprevalence (Figure) and Epstein–Barr nuclear antigen‐1 antibodies were higher in MS than control diseases. Additionally, the seroprevalences and frequencies of an intrathecal production of antibodies to EBV and other common viruses were investigated in patients with MS.