The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects.

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation / Iannetta, Marco; Zingaropoli, MARIA ANTONELLA; Bellizzi, Anna; Morreale, Manuela; Pontecorvo, Simona; D'Abramo, Alessandra; Oliva, Alessandra; Anzivino, Elena; Lo Menzo, Sara; D'Agostino, Claudia; Mastroianni, Claudio Maria; Millefiorini, Enrico; Pietropaolo, Valeria Antonietta; Francia, Ada; Vullo, Vincenzo; Ciardi, Maria Rosa. - In: PLOS ONE. - ISSN 1932-6203. - STAMPA. - 11:8(2016), pp. e0160277-e0160277. [10.1371/journal.pone.0160277]

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

ZINGAROPOLI, MARIA ANTONELLA;MORREALE, MANUELA;PONTECORVO, SIMONA;Oliva, Alessandra;D'AGOSTINO, Claudia;MASTROIANNI, Claudio Maria;MILLEFIORINI, Enrico;PIETROPAOLO, Valeria Antonietta;FRANCIA, Ada;VULLO, Vincenzo;CIARDI, Maria Rosa
2016

Abstract

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects.
2016
progressive multifocal leukoencephalopathy; human polyomavirus; virus-dna; steady-state; human-sera; prevalence; antibodies; infection; risk; pml
01 Pubblicazione su rivista::01a Articolo in rivista
Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation / Iannetta, Marco; Zingaropoli, MARIA ANTONELLA; Bellizzi, Anna; Morreale, Manuela; Pontecorvo, Simona; D'Abramo, Alessandra; Oliva, Alessandra; Anzivino, Elena; Lo Menzo, Sara; D'Agostino, Claudia; Mastroianni, Claudio Maria; Millefiorini, Enrico; Pietropaolo, Valeria Antonietta; Francia, Ada; Vullo, Vincenzo; Ciardi, Maria Rosa. - In: PLOS ONE. - ISSN 1932-6203. - STAMPA. - 11:8(2016), pp. e0160277-e0160277. [10.1371/journal.pone.0160277]
File allegati a questo prodotto
File Dimensione Formato  
Iannetta_T-cell-phenotype_2016.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.88 MB
Formato Adobe PDF
1.88 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/899274
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 17
social impact