A genetic variant of the anti-apoptotic protein Akt predicts natalizumab-induced lymphocytosis and post-natalizumab multiple sclerosis reactivation

Multiple Sclerosis : Clinical and Laboratory Research
S RossiD Centonze

Abstract

Multiple sclerosis (MS) patients discontinuing natalizumab treatment are at risk of disease reactivation. No clinical or surrogate parameters exist to identify patients at risk of post-natalizumab MS reactivation. To determine the role of natalizumab-induced lymphocytosis and of Akt polymorphisms in disease reactivation after natalizumab discontinuation. Peripheral leukocyte count and composition were monitored in 93 MS patients during natalizumab treatment, and in 56 of these subjects who discontinued the treatment. Genetic variants of the anti-apoptotic protein Akt were determined in all subjects because natalizumab modulates the apoptotic pathway and lymphocyte survival is regulated by the apoptotic cascade. Natalizumab-induced peripheral lymphocytosis protected from post-natalizumab MS reactivation. Subjects who relapsed or had magnetic resonance imaging (MRI) worsening after treatment cessation, in fact, had milder peripheral lymphocyte increases during the treatment, largely caused by less marked T cell increase. Furthermore, subjects carrying a variant of the gene coding for Akt associated with reduced anti-apoptotic efficiency (rs2498804T) had lower lymphocytosis and higher risk of disease reactivation. This study ident...Continue Reading

References

Dec 12, 1997·European Journal of Immunology·A SilvyT Defrance
Jan 28, 2004·Nature Genetics·Effat S EmamianJoseph A Gogos
May 25, 2005·Annals of Neurology·Antje KronerHeinz Wiendl
Nov 12, 2005·Annals of Neurology·Chris H PolmanJerry S Wolinsky
Apr 25, 2006·Annals of Neurology·Olaf StüveMichael K Racke
Apr 26, 2006·Current Neurology and Neuroscience Reports·Annette Langer-Gould, Lawrence Steinman
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Mar 26, 2008·Neurology·Robert J Fox, Ludwig Kappos
Feb 4, 2009·Neurology·Nicoline Schiess, Peter A Calabresi
Apr 2, 2009·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Lindsay M MortonPatricia Hartge
Jul 2, 2009·Expert Opinion on Biological Therapy·Frank NeumannRainer Haas
Jul 18, 2009·Journal of Neurology·Azza IsmailBasil Sharrack
Jul 21, 2009·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·N PutzkiV Limmroth
Sep 11, 2009·The New England Journal of Medicine·Hans LindåClaes Martin
Nov 13, 2009·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Giancarlo Comi
May 8, 2010·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Xia PuXifeng Wu
May 25, 2010·Lancet Neurology·Israel Steiner
Jul 28, 2010·Annals of Neurology·Joep KillesteinChris H Polman
Aug 26, 2010·Annals of Neurology·Leonid GorelikMeena Subramanyam
Sep 8, 2010·Annals of Neurology·Timothy W West, Bruce A C Cree
Sep 8, 2010·Annals of Neurology·Joseph R BergerTjalf Ziemssen
Dec 8, 2010·Multiple Sclerosis : Clinical and Laboratory Research·Michael D KaufmanH J Norton
Dec 24, 2010·Multiple Sclerosis : Clinical and Laboratory Research·Giovanni FrisulloAnna Paola Batocchi
May 10, 2011·Journal of Neuroimmunology·Mario SkaricaPeter A Calabresi
Jul 15, 2011·Journal of Neurophysiology·Francesco MoriDiego Centonze
Nov 9, 2011·Cell Cycle·Jonathan H Schatz, Hans-Guido Wendel

❮ Previous
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Citations

Feb 12, 2013·Expert Opinion on Biological Therapy·Mahmoud H Mosli, Brian G Feagan
Jul 6, 2014·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·M CapobiancoA Bertolotto
May 20, 2014·CNS Neuroscience & Therapeutics·Silvia RossiDiego Centonze
May 27, 2015·Revue neurologique·J-C CorvolL Lacomblez
May 18, 2016·International Journal of Molecular Sciences·Simona GranataGianluigi Zaza
Oct 11, 2015·Multiple Sclerosis : Clinical and Laboratory Research·E SignorielloG Lus
May 17, 2019·Expert Review of Neurotherapeutics·Laura De GiglioCarlo Pozzilli
Apr 9, 2019·Therapeutic Advances in Neurological Disorders·Luca ProsperiniSimone Fantaccini
Oct 10, 2020·Acta neurologica Belgica·Fatma Betul OktelikSuzan Cinar
Nov 18, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Jan KolcavaPavel Stourac
May 1, 2021·Journal of Personalized Medicine·María José Zarzuelo RomeroAlberto Jiménez Morales

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Methods Mentioned

BETA
flow cytometry
Assay

Software Mentioned

MassARRAY Assay Design

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