JC virus detection and JC virus-specific immunity in natalizumab-treated Multiple Sclerosis patients

<p>Abstract</p> <p>Background</p> <p>The use of natalizumab in multiple sclerosis (MS) may favour JC virus reactivation; this phenomenon is usually asymptomatic but can, albeit rarely, evolve into frank progressive multifocal leucoencephalopathy (PML).</p> <p>Methods</p> <p>JCV-specific CD8+ T lymphocytes were evaluated by flow cytometry over a 24-month period in 24 natalizumab-treated MS patients in whom JCV DNA was or was not detected in blood using quantitative real-time polymerase chain reaction; all these cases were asymptomatic.</p> <p>Results</p> <p>Perforin- and grazymes-containing VP-1-specific CD8+ T lymphocytes were reduced whereas CD107a-expressing cells were increased in JCV positive patients, suggesting an active degranulation of these cells; naïve CD8+ T lymphocytes were also decreased whereas memory cells were increased in patients in whom JCV reactivation was observed.</p> <p>Conclusion</p> <p>The presence of a CD8+ T lymphocyte-mediated effector immune response offers a greater insight into reactivation of JCV and its clinical sequelae, and may help the monitoring of patients on natalizumab therapy.</p

The chameleon of neuroinflammation:magnetic resonance imaging characteristics of natalizumab-associated progressive multifocal leukoencephalopathy

<p>Natalizumab is a monoclonal antibody against 4-integrin approved for the treatment of multiple sclerosis (MS) due to a positive effect on clinical and magnetic resonance imaging (MRI) outcome measures. However, one relatively rare but serious side effect of this drug is a higher risk of developing progressive multifocal leukoencephalopathy (PML). Since the FDA approval, more than 300 natalizumab-associated PML cases have been documented among more than 100,000 treated MS patients. MRI is a crucial tool in the surveillance of patients treated with natalizumab in order to detect possible signs of PML in the asymptomatic stage. Although classical imaging characteristics of PML are well established, MRI findings in natalizumab-associated PML, particularly in early disease stages, show rather new and heterogeneous imaging findings including different patterns of inflammation with contrast enhancement. This review provides a comprehensive overview of the heterogeneous imaging findings in natalizumab-associated PML in the context of the underlying pathophysiology, histopathology, and the diagnostic procedure. We describe the MRI patterns of PML lesion evolution and complications including immune reconstitution inflammatory syndrome (IRIS). Finally, we present guidelines to differentiate MRI findings in PML from inflammatory demyelinating lesions, to facilitate the early diagnosis of PML in patients treated with natalizumab.</p>