Anti-JCV Antibodies Detection and JCV DNA Levels in PBMC, Serum and Urine in a Cohort of Spanish Multiple Sclerosis Patients Treated with Natalizumab
Tóm tắt
One of the most effective multiple sclerosis (MS) treatment is natalizumab. Nevertheless, it has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML) caused by the JC virus (JCV). Our main objective was to assess the utility of testing JCV-DNA, apart from anti-JCV antibodies, to determine which natalizumab-treated MS patients has been previously in contact with the virus. For this purpose, 138 MS natalizumab/non-natalizumab treated patients participated in several studies. Cross-sectional study (CS): association of several epidemiological variables with anti-JCV antibodies and JCV-DNA levels in PBMC/serum/urine. First longitudinal study (A): evaluation of JCV-DNA prevalence in urine throughout the treatment. Second longitudinal study (B): simultaneous assessment of antibodies and viral DNA levels in PBMC/serum/urine at two time points. CS: The seropositivity rate for anti-JCV antibodies (62.3 %) and JCV prevalence in urine (59.4 %) were similar; although 26 % of our population was positive only using one of the two techniques. A: The viral prevalence in urine seemed to increase between the baseline visit and the others (Baseline-Visit/V18months, p = 0.006). B: Our rate of positive antibody seroconversion was 36 %. Nearly all patients with detectable JCV-DNA levels in PBMC excreted the virus intermittently in urine; while our PML case, positive in PBMC and serum samples 2 month before the PML, excreted JCV permanently. In conclusion, the determination of JCV DNA levels in urine could be complementary to anti-JCV antibodies for identifying MS patients who has been infected by the JCV. Further research would be necessary to understand the different JCV excretion profiles in urine.
Tài liệu tham khảo
Agostini HT, Ryschkewitsch CF, Stoner GL (1996) Genotype profile of human polyomavirus JC excreted in urine of immunocompetent individuals. J Clin Microbiol 34:159–164
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 366:1870–1880
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 361:1067–1074
Egli A, Infanti L, Dumoulin A, Buser A, Samaridis J, Stebler C, Gosert R, Hirsch HH (2009) Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis 199:837–846
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
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 9:264–272
Kitamura T, Aso Y, Kuniyoshi N, Hara K, Yogo Y (1990) High incidence of urinary JC virus excretion in nonimmunosuppressed older patients. J Infect Dis 161:1128–1133
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 71:115–123
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, Palu G, Uccelli A, Mancardi GL, Varnier OE (2012) Urinary JCV-DNA testing during natalizumab treatment may increase accuracy of PML risk stratification. J Neuroimmune Pharmacol 7:665–672
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 57:141–146
Ling PD, Lednicky JA, Keitel WA, Poston DG, White ZS, Peng R, Liu Z, Mehta SK, Pierson DL, Rooney CM, Vilchez RA, Smith EO, Butel JS (2003) The dynamics of herpesvirus and polyomavirus reactivation and shedding in healthy adults: a 14-month longitudinal study. J Infect Dis 187:1571–1580
Major EO (2010) Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies. Annu Rev Med 61:35–47
Mancuso R, Saresella M, Hernis A, Marventano I, Ricci C, Agostini S, Rovaris M, Caputo D, Clerici M (2012) JC virus detection and JC virus-specific immunity in natalizumab-treated multiple sclerosis patients. J Transl Med 10:248
Matos A, Duque V, Beato S, da Silva JP, Major E, Melico-Silvestre A (2010) Characterization of JC human polyomavirus infection in a Portuguese population. J Med Virol 82:494–504
Perkins MR, Ryschkewitsch C, Liebner JC, Monaco MC, Himelfarb D, Ireland S, Roque A, Edward HL, Jensen PN, Remington G, Abraham T, Abraham J, Greenberg B, Kaufman C, Laganke C, Monson NL, Xu X, Frohman E, Major EO, Douek DC (2012) Changes in JC virus-specific T cell responses during natalizumab treatment and in natalizumab-associated progressive multifocal leukoencephalopathy. PLoS Pathog 8:e1003014
Reid CE, Li H, Sur G, Carmillo P, Bushnell S, Tizard R, McAuliffe M, Tonkin C, Simon K, Goelz S, Cinque P, Gorelik L, Carulli JP (2011) Sequencing and analysis of JC virus DNA from natalizumab-treated PML patients. J Infect Dis 204:237–244
Rinaldi L, Rinaldi F, Perini P, Calabrese M, Seppi D, Grossi P, Mattisi I, Barzon L, Mengoli C, Sanzari M, Palu 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 81:1345–1350
Rossi A, Delbue S, Mazziotti R, Valli M, Borghi E, Mancuso R, Calvo MG, Ferrante P (2007) Presence, quantitation and characterization of JC virus in the urine of Italian immunocompetent subjects. J Med Virol 79:408–412
Rudick RA, O’Connor PW, Polman CH, Goodman AD, Ray SS, Griffith NM, Jurgensen SA, Gorelik L, Forrestal F, Sandrock AW, Goelz E (2010) Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Ann Neurol 68:304–310
Sadiq SA, Puccio LM, Brydon EW (2010) JCV detection in multiple sclerosis patients treated with natalizumab. J Neurol 257:954–958
Trampe AK, Hemmelmann C, Stroet A, Haghikia A, Hellwig K, Wiendl H, Goelz S, Ziegler A, Gold R, Chan A (2012) Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort. Neurology 78:1736–1742
Watzinger F, Suda M, Preuner S, Baumgartinger R, Ebner K, Baskova L, Niesters HG, Lawitschka A, Lion T (2004) Real-time quantitative PCR assays for detection and monitoring of pathogenic human viruses in immunosuppressed pediatric patients. J Clin Microbiol 42:5189–5198