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Open Access Research

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

Roberta Mancuso1*, Marina Saresella1, Ambra Hernis1, Ivana Marventano1, Cristian Ricci1, Simone Agostini12, Marco Rovaris1, Domenico Caputo1 and Mario Clerici12

Author Affiliations

1 Don C. Gnocchi Foundation, ONLUS, Milan, Italy

2 Department of Physiopathology and Transplantation, University of Milan, Milan, Italy

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Journal of Translational Medicine 2012, 10:248  doi:10.1186/1479-5876-10-248

Published: 11 December 2012

Abstract

Background

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).

Methods

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.

Results

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.

Conclusion

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.

Keywords:
Cell mediated immunity; Natalizumab; MS