title: Immunological Markers for PML Prediction in MS Patients Treated with Natalizumab.
abstract: Natalizumab (NTZ), a monoclonal antibody recognizing the alpha4 integrin chain, has been approved for the treatment of active multiple sclerosis, but expose to the onset of a rare side effect, progressive multifocal leukoencephalopathy (PML). Estimating the individual risk of PML in NTZ-treated patients is a major challenge, and therapeutic strategies are mainly guided by the overall PML risk assessed by identified risk factors: JC virus (JCV) seropositivity, treatment duration (with peak incidence after 24 months), and the previous use of immunosuppressive therapies. Given that this stratification does not yet allow a precise individual prediction of PML, other predictive markers are needed, and several immunological biomarkers have been described. Quantification of anti-JCV antibody levels may improve individual predictive value, with higher baseline titers indicating increased risk. Other immunological biomarkers such as leukocyte cell membrane markers (CD49d, CD11a, and CD62L), detection of circulating JCV-specific activated T effector memory cells (TEM) or genetic screening have been proposed. In this review, we discuss how recent progress in immunology has paved the way for «new combined monitoring», which will include immunological screening, in NTZ-treated patients.
authors.affiliation: AP-HP, Hôpital Saint-Antoine , Paris , France ; Centre Hospitalier Universitaire de Dijon, Université de Bourgogne , Dijon , France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Antoniol
authors.affiliation: AP-HP, Hôpital Saint-Antoine , Paris , France ; Sorbonne Universités, Université Pierre et Marie Curie, UMR S 1127, CNRS UMR 7225, and l'Institut du Cerveau et de la Moelle Épinière (ICM) , Paris , France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
keywords: JC virus; PML; effector memory T-cells; multiple sclerosis; risk stratification; selectin