Journal Article FZJ-2024-03591

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

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2024
Elsevier Amsterdam [u.a.]

Multiple Sclerosis and Related Disorders 87, 105664 - () [10.1016/j.msard.2024.105664]

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Abstract: Background: Natalizumab is an effective treatment for relapsing multiple sclerosis (MS). During therapy, individualsare at increased risk of developing progressive multifocal leukoencephalopathy (PML). So far, therelevant reservoir for PML-type JC polyomavirus (JCV) remains elusive. We here tested if the detection of JCVDNAin 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 andknown 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-associatedvariants by sequencing.Results: Thirty MS patients treated with natalizumab were screened. For 21 patients, blood, stool, and urinesamples 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 thewhole blood or stool samples. Four urine samples had measurable JCV-DNA, ranging from 1.71×104–1.07×108international units (IU)/mL detected by RT-PCR, corresponding to 4.62×104–9.85×106 copies/mL measured byddPCR. 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 ofddPCR and RT- PCR was comparable. Our findings do not support assessing stool samples for PML risk stratificationin persons with MS. Further studies are needed to explore where PML-associated viral variants arise.

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Contributing Institute(s):
  1. Kognitive Neurowissenschaften (INM-3)
Research Program(s):
  1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)
  2. DFG project 501362249 - Progressive multifokale Leukenzephalopathie: Biomarker für eine frühzeitige Diagnose, für die Risikovorhersage unter Immuntherapien sowie für ein Ansprechen auf eine zielgerichtete Therapie (501362249) (501362249)

Appears in the scientific report 2024
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Medline ; Creative Commons Attribution CC BY 4.0 ; OpenAccess ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2024-06-06, last modified 2025-02-04


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