Absence of JC polyomavirus in stool samples of patients with multiple sclerosis despite high anti-JCV antibodies in serum

Finja Schweitzer; Anne Ladwig; Sarah Opala; Sarah Laurent; Michael Schroeter; Susan Goelz; Gereon R Fink; Ulrike Wieland; Steffi Silling; Clemens Warnke

doi:10.1016/j.msard.2024.105664

Absence of JC polyomavirus in stool samples of patients with multiple sclerosis despite high anti-JCV antibodies in serum

Mult Scler Relat Disord. 2024 May 5:87:105664. doi: 10.1016/j.msard.2024.105664. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
² Oregon Health and Sciences University, Portland, OR, USA.
³ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Jülich, Jülich, Germany.
⁴ National Reference Center for Papilloma- and Polyomaviruses, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁵ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. Electronic address: clemens.warnke@uk-koeln.de.

PMID: 38735204
DOI: 10.1016/j.msard.2024.105664

Abstract

Background: Natalizumab is an effective treatment for relapsing multiple sclerosis (MS). During therapy, individuals are at increased risk of developing progressive multifocal leukoencephalopathy (PML). So far, the relevant reservoir for PML-type JC polyomavirus (JCV) remains elusive. We here tested if the detection of JCV-DNA in stool of persons with MS treated with natalizumab could be a future tool for PML risk assessment.

Methods: The presence of JCV-DNA in stool, urine, and whole blood of MS patients treated with natalizumab and known serum anti-JCV antibodies index values (IV) was studied. Different DNA extraction methods, real-time (RT) and droplet digital (dd) PCR techniques were compared. JCV isolates were screened for PML-associated variants by sequencing.

Results: Thirty MS patients treated with natalizumab were screened. For 21 patients, blood, stool, and urine samples were available. These patients were stratified according to their serum anti-JCV antibody IV (high (>1.5, n = 12); medium (1.5-0.9, n = 2); low (<0.9, n = 1); negative (n = 6)). JCV-DNA could not be detected in the whole blood or stool samples. Four urine samples had measurable JCV-DNA, ranging from 1.71×10⁴-1.07×10⁸ international units (IU)/mL detected by RT-PCR, corresponding to 4.62×10⁴-9.85×10⁶ copies/mL measured by ddPCR. All JCV variants were wild-type and derived from patients with high antibody IV.

Conclusion: Stool-specific DNA extraction methods provided the highest quality of DNA, while the sensitivity of ddPCR and RT- PCR was comparable. Our findings do not support assessing stool samples for PML risk stratification in persons with MS. Further studies are needed to explore where PML-associated viral variants arise.

Keywords: Gut; JCPyV; JCV; MS; PML; Reservoir.