JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients

详细信息    查看全文

• 作者：Serena Delbue ; Francesca Elia ; Camilla Carloni…
• 关键词：Natalizumab ; JC virus ; Multiple sclerosis ; Urinary excretion ; Seroprevalence
• 刊名：Journal of NeuroVirology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：21
• 期：6
• 页码：645-652
• 全文大小：716 KB
• 参考文献：Berger JR, Khalili K (2012) The pathogenesis of progressive multifocal leukoencephalopathy. Discov Med 12:495-03
  Berger JR, Houff SA, Gurwell J, Vega N, Miller CS, Danaher RJ (2013) JC virus antibody status underestimates infection rates. Ann Neurol 74:84-0PubMedCentral CrossRef PubMed
  Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz 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 366:1870-880CrossRef PubMed
  Chen Y, Bord E, Tompkins T, Miller J, Tan CS, Kinkel RP, Stein MC, Viscidi RP, Ngo LH, Koralnik IJ (2009) Asymptomatic reactivation of JC virus in patients treated with natalizumab. N Engl J Med 361:1067-074PubMedCentral CrossRef PubMed
  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 9:438-46CrossRef PubMed
  Delbue S, Sotgiu G, Fumagalli D, Valli M, Borghi E, Mancuso R, Marchioni E, Maserati R, Ferrante P (2005) A case of a PML patient with four different JC virus TCR rearrangements in CSF, blood, serum and urine. J Neurovirol 11:51-7CrossRef PubMed
  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 13:77-8
  Derfuss T, Kappos L (2013) Predicting PML in natalizumab-treated patients: can we do better? J Neurol Neurosurg Psychiatry 84:1182-183CrossRef PubMed
  Dominguez-Mozo MI, Garcia-Montojo M, De Las HV et al (2013) Anti-JCV antibodies detection and JCV DNA levels in PBMC, serum and urine in a cohort of Spanish multiple sclerosis patients treated with natalizumab. J NeuroImmune Pharm 8:1277-6CrossRef
  D?rries K, Vogel E, Günther S, Czub S (1994) Infection of human polyomaviruses JC and BK in peripheral blood leukocytes from immunocompetent individuals. Virology 198:59-0CrossRef PubMed
  Ferrante P, Caldarelli-Stefano R, Omodeo-Zorini E, Mediati M, Fainardi E, Granieri E, Caputo D (1997) Comprehensive investigation of the presence of JC virus in AIDS patients with and without progressive multifocal leukoencephalopathy. J Med Virol 52:235-42CrossRef PubMed
  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 68:295-03CrossRef PubMed
  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 9:264-2CrossRef PubMed
  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, S?rensen PS, King J (2011) Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol 10:745-58CrossRef PubMed
  Knowles WA, Pipkin P, Andrews N, Vyse A, Minor P, Brown DW, Miller E (2003) Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol 71:115-23CrossRef PubMed
  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 7:665-72CrossRef
  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 57:141-46CrossRef PubMed
  Lonergan R, Carr M, De Gascun C, Costelloe LF, Waters A, Coughlan S, Duggan M, Doyle K, Jordan S, Hutchinson MW, Hall WW, Tubridy NJ (2009) Reactivation of BK polyomavirus in patients with multiple sclerosis receiving natalizumab therapy. J Neurovirol 15:351-59CrossRef PubMed
  Major EO (2010) Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies. Annu Rev Med 61:35-7CrossRef PubMed
  Major EO, Frohman E, Douek D (2013a) JC viremia in natalizumab-treated patients with multiple sclerosis. N Engl J Med 368:2240-241PubMedCentral CrossRef PubMed
  Major EO, Frohman E, Douek D (2013b) M
• 作者单位：Serena Delbue (1)
  Francesca Elia (2)
  Camilla Carloni (1)
  Valentina Pecchenini (1)
  Diego Franciotta (3)
  Matteo Gastaldi (3)
  Elena Colombo (3)
  Lucia Signorini (1)
  Silvia Carluccio (1)
  Anna Bellizzi (4)
  Roberto Bergamaschi (3)
  Pasquale Ferrante (1) (5)
  
  1. Department of Biomedical Surgical and Dental Sciences, University of Milano, Via Pascal, 36, Milan, 20133, Italy
  2. Laboratory of Translational Research Fondazione Ettore Sansavini, Lugo, Italy
  3. Department of General Neurology, National Neurological Institute C. Mondino, Pavia, Italy
  4. Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy
  5. Istituto Clinico Città Studi, Milan, Italy
  
• 刊物主题：Neurosciences; Virology; Infectious Diseases; Immunology; Neurology;
• 出版者：Springer US
• ISSN：1538-2443

文摘

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--.04), but not for BKV (p--.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. Keywords Natalizumab JC virus Multiple sclerosis Urinary excretion Seroprevalence