title: Divergent Trends of Anti-JCPyV Serum Reactivity and Neutralizing Activity in Multiple Sclerosis (MS) Patients during Treatment with Natalizumab.
abstract: The association between natalizumab and progressive multifocal leukoencephalopathy (PML) is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV) neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24), when progressive multifocal leukoencephalopathy (PML) risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039), not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239). This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097), a further decrease of the neutralizing activity was observed (p = 0.0062). This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment.
authors.affiliation: Laboratorio di Microbiologia e Virologia, Università "Vita-Salute" San Raffaele, Milan 20132, Italy. diotti.robertaantonia@hsr.it.
authors.forename: Roberta Antonia
authors.initials: RA
authors.lastname: Diotti
authors.affiliation: Multiple Sclerosis Center, Spedali Civili of Brescia, Brescia 25123, Italy. ruggero.capra@gmail.com.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Capra
authors.affiliation: Neurological Department, IRCCS Hospital San Raffaele, Milan 20132, Italy. moiola.lucia@hsr.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Moiola
authors.affiliation: Laboratorio di Microbiologia e Virologia, Università "Vita-Salute" San Raffaele, Milan 20132, Italy. caputo.vlr@gmail.com.
authors.forename: Valeria
authors.initials: V
authors.lastname: Caputo
authors.affiliation: Multiple Sclerosis Center, Spedali Civili of Brescia, Brescia 25123, Italy. ncl.derossi@gmail.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: De Rossi
authors.affiliation: Neurological Department, IRCCS Hospital San Raffaele, Milan 20132, Italy. sangalli.francesca@hsr.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sangalli
authors.affiliation: Neurological Department, IRCCS Hospital San Raffaele, Milan 20132, Italy. martinelli.vittorio@hsr.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: Laboratorio di Microbiologia e Virologia, Università "Vita-Salute" San Raffaele, Milan 20132, Italy. burioni.roberto@hsr.it.|Ospedale San Raffaele, Milan 20132, Italy. burioni.roberto@hsr.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Burioni
authors.affiliation: Laboratorio di Microbiologia e Virologia, Università "Vita-Salute" San Raffaele, Milan 20132, Italy. clementi.massimo@hsr.it.|Ospedale San Raffaele, Milan 20132, Italy. clementi.massimo@hsr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.affiliation: Laboratorio di Microbiologia e Virologia, Università "Vita-Salute" San Raffaele, Milan 20132, Italy. mancini.nicasio@hsr.it.|Ospedale San Raffaele, Milan 20132, Italy. mancini.nicasio@hsr.it.
authors.forename: Nicasio
authors.initials: N
authors.lastname: Mancini
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D036022:Capsid Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007577:JC Virus / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D000069442:Natalizumab / Q000627:therapeutic use*; D010865:Pilot Projects; D011446:Prospective Studies; D044967:Serum / Q000737:chemistry; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D007155:Immunologic Factors; D000069442:Natalizumab; C062481:VP1 protein, polyomavirus
keywords: humoral response; multiple sclerosis; natalizumab; progressive multifocal leukoencephalopathy