The risk of developing progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis (MS) patients is related to serum anti-JCV antibody (JCVAb) index. However, the correlation of JCVAb index with other disease-modifying treatments (DMTs) is not well understood.
In this study, we investigated the JCVAb seropositivity rate/JCVAb indexes and its correlation with clinical profiles in Japanese MS patients, and the relationship between JCVAb indexes and DMTs.
JCVAb indexes were measured in 149 serum samples from 105 patients with MS. JCVAb indexes and seropositivity, and their correlation with age, sex, disease duration, Kurtzke expanded disability status scale and the duration of the DMTs were evaluated in each patient.
JCVAb was positive in 73 of 105 MS patients. Within 40 fingolimod-treated patients, 27 were positive for JCVAb and JCVAb indexes were positively correlated with the duration of fingolimod treatment. No significant relation was found between JCVAb indexes and the duration of treatment for the other disease-modifying drugs.
JCVAb seropositivity was comparatively high in Japanese MS patients. Fingolimod treatment is likely to increase serum JCVAb index, possibly leading to the development of PML. Therefore, it is advised that JCVAb index should be serially monitored during fingolimod treatment to decrease PML risk.
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Kurtzke expanded disability status scale
John Cunningham virus
Progressive multifocal leukoencephalopathy
Clifford DB, De Luca A, Simpson DM, Arendt G, Giovannoni G, Nath A (2010) Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. Lancet Neurol 9:438–446
Ho PR, Koendgen H, Campbell N, Haddock B, Richman S, Chang I (2017) Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol 11:925–933
Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goeltz S, Natarajan A, Lee S, Plavina T, Scanlon JV, Sandrock A, Bozic C (2012) Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 366:1870–1880
Plavina T, Subramanyam M, Bloomgren G, Richman S, Pace A, Lee S, Schlain B, Campagnolo D, Belachew S, Ticho B (2014) Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol 76:802–812
Bozic C, Richman S, Plavina T, Natarajan A, Scanlon JV, Subramanyam M, Sandrock A, Bloomgren G (2011) Anti-John Cunningham virus antibody prevalence in multiple sclerosis patients: baseline results of STRATIFY-1. Ann Neurol 70:742–750
Rosenkranz T, Novas M, Terborg C (2015) PML in a patient with lymphocytopenia treated with dimethyl fumarate. N Engl J Med 372:1476–1478
Baharnoori M, Lyons J, Dastagir A, Koralnik I, Stankiewicz JM (2016) Nonfatal PML in a patient with multiple sclerosis treated with dimethyl fumarate. Neurol Neuroimmunol Neuroinflamm 3:e274
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O’Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2010) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2011):292–302
Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452
Gorelik L, Lerner M, Bixler S, Crossman M, Schlain B, Simon K, Pace A, Cheung A, Chen LL, Berman M, Zein F, Wilson E, Yednock T, Sandrock A, Goelz SE, Subramanyam M (2010) Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol 68:295–303
Sroller V, Hamšíková E, Ludvíková V, Vochozková P, Kojzarová M, Fraiberk M, Saláková M, Morávková A, Forstová J, Němečková S (2014) Seroprevalence rates of BKV, JCV, and MCPyV polyomaviruses in the general Czech Republic population. J Med Virol 86:1560–1568
Antonsson A, Green AC, Mallitt KA, O’Rourke PK, Pawlita M, Waterboer T, Neale RE (2010) Prevalence and stability of antibodies to the BK and JC polyomaviruses: a long-term longitudinal study of Australians. J Gen Virol 91:1849–1853
Cambron M, Hadhoum N, Duhin E, Lacour A, Chouraki A, Vermersch P (2017) JCV serology in time: 3 years of follow-up. Acta Neurol Scand 136:54–58
Taguchi F, Kajioka J, Miyamura T (1982) Prevalence rate and age of acquisition of antibodies against JC virus and BK virus in human sera. Microbiol Immunol 26:1057–1064
Tanaka M, Kinoshita M, Tanaka K (2015) Anti-John Cunningham virus index in Japanese patients with multiple sclerosis and neuromyelitis optica-related disorder. Clin Exp Neuroimmunol 6:309–311
Bozic C, Subramanyam M, Richman S, Plavina T, Zhang A, Ticho B (2014) Anti-JC virus (JCV) antibody prevalence in the JCV Epidemiology in MS (JEMS) trial. Eur J Neurol 21:299–304
Paz SC, Branco LP, Pereira MAC, Spessotto CV, Fragoso YD (2018) Systematic review of published data on the worldwide prevalence of John Cunningham virus (JCV) in patients with multiple sclerosis. Epidemiol Health (in press)
Gyang TV, Hamel J, Goodman AD, Gross RA, Samkoff L (2016) Fingolimod-associated PML in a patient with prior immunosuppression. Neurology 86:1843–1845
Killestein J, Vennegoor A, van Golde AE, Bourez RL, Wijilens ML, Wattjes MP (2014) PML-IRIS during fingolimod diagnosed after natalizumab discontinuation. Case Rep Neurol Med 2014:Article ID 307872
Sinnecker T, Othman J, Kühl M, Metz I, Niendorf T, Kunkel A, Paul F, Wuerfel J, Faiss J (2016) Progressive multifocal leukoencephalopathy in a multiple sclerosis patient diagnosed after switching from natalizumab to fingolimod. Case Rep Neurol Med 2016:5876798
Raffel J, Gafson AR, Malik O, Nicholas R (2015) Anti-JC virus antibody titres increase over time with natalizumab treatment. Mult Scler 21:1833–1838
Peters J, Williamson E (2017) Natalizumab therapy is associated with changes in serum JC virus antibody indices over time. J Neurol 264:2409–2412
Schwab N, Schneider-Hohendorf T, Pignolet B, Breuer J, Gross CC, Göbel K, Brassat D, Wiendl H (2016) Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. Neurol Neuroimmunol Neuroinflamm 3:e195
Javed A, Reder AT (2016) Rising JCV-Ab index during natalizumab therapy for MS: inauspicious for a highly efficacious drug. Neurol Neuroimmunol Neuroinflamm 3:e199
Subei AM, Cohen JA (2015) Sphingosine 1-phosphate receptor modulators in multiple sclerosis. CNS Drugs 29:565–575
Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, Allende ML, Proia RL, Cyster JG (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355–360
Part of this study was presented in a poster session at the 23rd WCN (World Congress of Neurology) held in Kyoto, Japan (September 2017).
All patients provided informed consent prior to their inclusion to this study.
Conflicts of interest
The authors declare no conflicts of interest.
Ethical standard statement
This study was approved by the Ethics Committee of Chiba University School of Medicine (No.842) and all participants provided written informed consent.
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Aoyama, S., Mori, M., Uzawa, A. et al. Serum anti-JCV antibody indexes in Japanese patients with multiple sclerosis: elevations along with fingolimod treatment duration. J Neurol 265, 1145–1150 (2018). https://doi.org/10.1007/s00415-018-8813-z