Disease Modifying Therapies – Risk Management Poster Presentation

P0346 - Is the gut a relevant reservoir for persistent JCPyV infection? (ID 1327)

Speakers
  • F. Schweitzer
Authors
  • F. Schweitzer
  • A. Ladwig
  • S. Laurent
  • M. Schroeter
  • S. Goelz
  • U. Wieland
  • S. Silling
  • C. Warnke
Presentation Number
P0346
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Natalizumab is an effective therapy for treatment of relapsing multiple sclerosis (MS). A serious side effect of natalizumab treatment is the occurrence of progressive multifocal leukoencephalopathy (PML) associated with JC polyomavirus (JCPyV) infection. A large fraction (20-30%) of individuals shed JCPyV DNA of wildtype variants in urine, yet around 50% of patients with the detection of anti-JCPyV antibodies in blood do not. PML-type JCPyV DNA variants have not been found in urine. Thus, the relevant reservoir of JCPyV remains unknown. We hypothesize that the gut may be this relevant reservoir and that natalizumab might alter the adaptive immunity in the gut. This could result in an increase in viral replication which would, in turn, facilitate viral genome alterations potentially inducing the formation of JCVPyV PML-type variants.

Objectives

Assessment of the gut as a potential reservoir for JC polyomavirus, associated with the development of progressive multifocal leukoencephalopathy.

Methods

The presence of JCPyV DNA in stool, urine and EDTA blood of natalizumab-treated MS patients (n=27; 22 female, 5 male) with known anti-JCPyV antibody index values in blood was assessed: antibody index above 1.5 (n=13), antibody index 1.5-0.9 (n=4), antibody index below 0.9 (n=4) and 6 with no detection of anti-JCPyV antibodies. Different DNA extraction methods and PCR techniques were applied and assay sensitivities assured performing spiking experiments.

Results

JCPyV DNA could not be detected in any of the EDTA blood or stool samples. Four urine samples had detectable JCPyV viral load, ranging from 4,500-427,000 copies/mL. All of these samples derived from patients with high antibody index values (>1.5).

Conclusions

The gut is either not the relevant reservoir for PML-associated JCPyV, or stool samples taken at a single occasion are not appropriate to test the hypothesis of JCPyV infection of the gut. As in our cohort the proportion of patients with detectable JCPyV DNA in urine was comparably low, further studies are ongoing validating our results, and improving sensitivity of the JCPyV PCR protocol from stool specimens.

Collapse