Background: Progressive multifocal leukoencephalopathy (PML) is
associated with natalizumab treatment in patients with multiple sclerosis (MS).
It has been hypothesized that natalizumab mobilizes JC virus (JCV)-infected
haematopoietic progenitor cells mediating viraemia and subsequently this
disease.
Objective: The objective of this study was to investigate peripheral
haematopoietic progenitor cells for evidence of JCV DNA in MS patients treated
with natalizumab.
Methods: We assessed JCV and cytomegalovirus (CMV) DNA in
magnetically separated CD34+ haematopoietic progenitor cells,
peripheral blood mononuclear cells and plasma of 67 natalizumab-treated patients
with MS and six PML patients.
Results: Viral DNA was not detectable in CD34+
haematopoietic progenitor or peripheral blood mononuclear cells from any sample.
Two plasma samples from patients with MS while undergoing natalizumab treatment
were JCV-positive. In one case clinically manifest PML developed 8 months
thereafter.
Conclusions: Our findings do not support the hypothesis that
natalizumab mobilizes JC virus-infected CD34+ cells from the bone
marrow mediating JC viraemia. Notably, JC viraemia was detected in one patient
with MS prior to developing clinical PML. This warrants further study.