JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients
- First Online:
- 388 Downloads
The risk of developing progressive multifocal leukoencephalopathy (PML), as a consequence of infection/reactivation with JC virus (JCV), is consistent in natalizumab-treated multiple sclerosis (MS) patients, with 430 cases of PML reported so far. The risk of PML is higher in JCV seropositive patients, and it is recommended that only MS patients without JCV antibodies should be enrolled in the treatment postulating that they do not have JCV infection.
We have studied forty-two natalizumab-treated MS patients, and urine and blood were collected monthly for up to 60 months. JCV and BK virus (BKV) DNA presence was verified using quantitative real-time PCR assays, and serum anti-JCV antibodies were measured with the Stratify and/or Stratify DxSelect tests.
JCV and BKV DNA were not found in the blood samples, whereas they were found at least once in the urine of 21 of 42 (50 %) and of 25/42 (59.5 %) patients, respectively. JCV DNA urinary shedding increased up to month 24 of natalizumab treatment (45.2 %), and the effect of time was significant for JCV (p = 0.04), but not for BKV (p = 0.39). JCV viruria and seropositivity did not completely correlate, since three patients shedding JCV DNA in the urine were seronegative according to the serological tests.
The results indicated that natalizumab therapy may increase the rate of JCV urinary shedding. Additionally, we confirmed that the identification of JCV carriers cannot solely rely on serological tests, but sensitive methods for viral DNA detection should be adopted to more precisely identify the truly JCV uninfected cases.
KeywordsNatalizumab JC virus Multiple sclerosis Urinary excretion Seroprevalence
- Berger JR, Khalili K (2012) The pathogenesis of progressive multifocal leukoencephalopathy. Discov Med 12:495–503Google Scholar
- Delbue S, Guerini F, Mancuso R, Caputo D, Mazziotti R, Saresella M, Ferrante P (2007) JCV viremia in interferon-beta treated and untreated Italian multiple sclerosis patients and healthy controls. J Neurovirol 13:77–78Google Scholar
- Jilek S, Jaquiery E, Hirsch HH, Lysandropoulos A, Canales M, Guignard L, Schluep M, Pantaleo G, Du Pasquier RA (2010) Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study. Lancet Neurol 9:264–72CrossRefPubMedGoogle Scholar
- Kappos L, Bates D, Edan G, Eraksoy M, Garcia-Merino A, Grigoriadis N, Hartung HP, Havrdová E, Hillert J, Hohlfeld R, Kremenchutzky M, Lyon-Caen O, Miller A, Pozzilli C, Ravnborg M, Saida T, Sindic C, Vass K, Clifford DB, Hauser S, Major EO, O'Connor PW, Weiner HL, Clanet M, Gold R, Hirsch HH, Radü EW, Sørensen PS, King J (2011) Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol 10:745–758CrossRefPubMedGoogle Scholar
- Laroni A, Giacomazzi CG, Grimaldi L, Gallo P, Sormani MP, Bertolotto A, McDermott JL, Gandoglia I, Martini I, Vitello G, Rinaldi F, Barzon L, Militello V, Pizzorno M, Bandini F, Capello E, Palù G, Uccelli A, Mancardi GL, Varnier OE (2012) Urinary JCV-DNA testing during natalizumab treatment may increase accuracy of PML risk stratification. J NeuroImmune Pharm 7:665–672CrossRefGoogle Scholar
- Lee P, Plavina T, Castro A, Berman M, Jaiswal D, Rivas S, Schlain B, Subramanyam M (2013) A second-generation ELISA (STRATIFY JCV DxSelect) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification. J Clin Virol 57:141–146CrossRefPubMedGoogle Scholar
- Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW, Investigators AFFIRM (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899CrossRefPubMedGoogle Scholar
- Rinaldi L, Rinaldi F, Perini P, Calabrese M, Seppi D, Grossi P, Mattisi I, Barzon L, Mengoli C, Sanzari M, Palú G, Gallo P (2010) No evidence of JC virus reactivation in natalizumab treated multiple sclerosis patients: an 18 month follow-up study. J Neurol Neurosurg Psychiatry 81:1345–1350CrossRefPubMedGoogle Scholar
- TYSABRI Safety Update. (2014) (Accessed January, 2014, at https://medinfo.biogenidec.com/medinfo/secure/pmlresource.do?resource=TYSABRIPMLSafetyUpdate)