Progresivní multifokální leukoencefalopatie – epidemiologie, imunitní odpověď, klinické rozdíly, léčba

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Autoři: S. Snopková ¹; P. Štourač ²; L. Fašaneková ¹; M. Mihalčin ¹; K. Havlíčková ¹; R. Svačinka ¹; P. Volfová ³; P. Snopek ⁴; P. Husa ¹
Působiště autorů: Klinika infekčních chorob FN Brno a LF MU, Brno ¹; Neurologická klinika FN Brno a LF MU, Brno ²; Interní hematoonkologická klinika FN Brno a LF MU, Brno ³; Fakulta humanitních studií UTB, Zlín ⁴
Vyšlo v časopise: Epidemiol. Mikrobiol. Imunol. 68, 2019, č. 1, s. 24-31
Kategorie: Souhrnné sdělení

Souhrn

Progresivní multifokální leukoencefalopatie (PML) je závažné onemocnění centrální nervové soustavy s velmi vysokou mortalitou. Příčinou onemocnění je JC virus s vysokou séroprevalencí dosahující až 80 %. PML je typické oportunní onemocnění vyskytující se zejména u syndromu získané imunodeficience u pacientů s hlubokým imunodeficitem. Počet případů PML se však v posledních letech zvyšuje také u všeobecné populace jako důsledek vysoce účinných imunosupresivních a imunomodulačních léčebných postupů. V tomto článku autoři uvádějí virologické a epidemiologické souvislosti a charakteristické projevy PML. Jsou diskutovány možné vztahy humorální a buněčné imunity a jsou zmíněny omezené možnosti léčby včetně profylaxe.

Klíčová slova:

buněčná imunita – poměr CD4/CD8 – sclerosis multiplex – progresivní multifokální leukoencefalopatie

Zdroje

1. Hoffmann C. Opportunistic infections. In: Hoffmann C, Rockstroh JK. HIV 2015/2016. Hamburg: Medizin Fokus Verlag; 2015. pp. 377–380.

2. Smolle E, Trojan A, Schuster SJ, et al. Progressive multifocal leukoencephalopathy – a case report and review of the literature. In Vivo, 2014;28(5):941–948.

3. Sudhakar P, Bachman DM, Mark AS, et al. Progressive multifocal leukoencephalopathy: recent advances and a neuro-ophthalmological review. J Neuroophthalmol, 2015;35(3):296–305.

4. Bauer J, Gold R, Adams O, et al. Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome (IRIS). Acta Neuropathol, 2015;130(6):751–764.

5. Koralnik IJ, Wuthrich C, Dang X, et al. JC virus granule cell neuronopathy: a novel clinical syndrome distinct from progressive multifocal leukoencephalopathy. Ann Neurol, 2005;57(4):576–580.

6. Wuthrich C, Dang X, Westmoreland S, et al. Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neurons. Ann Neurol, 2009;65(6):742–748.

7. Shin J, Phelan PJ, Chhum P, et al. Analysis of JC virus DNA replication using a quantitative and high-throughput assay. Virology, 2014;468-470:113–125.

8. Rozsypal H, Jilich D, Hubacek P, et al. Úskalí diagnostiky progresivní multifokální leukoencefalopatie u pacientů infikovaných lidským virem imunodeficience – kazuistiky. Cesk Slov Neurol N, 2013;76/109(4):501–507.

9. Bellizzi A, Anzivino E, Rodio DM, et al. New insight on human polyomavirus JC and pathogenesis of progressive multifocal leukoencephalopathy. Clin Dev Immunol, 2013;2013:839719 [cit. 2017-12-12]. Dostupné na www: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652120/

10. Delbue S, Elia F, Carloni C, et al. JC virus load in cerebrospinal fluid and transcriptional control region rearrangements may predict the clinical course of progressive multifocal leukoencephalopathy. J Cell Physiol, 2012;227(10):3511–3517.

11. Mateen FJ, Muralidharan R, Carone M, et al. Progressive multifocal leukoencephalopathy in transplant recipients. Ann Neurol, 2011;70:305–322.

12. Augusto L, Neves N, Reis C, et al. Clinical and radiological characterization of progressive multifocal leukoencephalopathy in HIV-infected patients: A retrospective analysis and review of the literature. Acta Med Port, 2015;28(3):286–296.

13. US Food and Drug Administration (2014): Drug safety and availability – FDA Drug Safety Communication: FDA warns about rare case of brain infection PML with MS drug Tecfidera (dimethyl fumarate) [cit. 2017-04-10]. Dostupné na www: http://www.fda.gov./Drugs/DrugSafety/ucm.424625.htm

14. Ermis U, Weis J, Schulz JB. PML in a patient treated with fumaric acid. N Engl J Med, 2013;368(17):1657–1658.

15. Linda H, von Heijne A Major EO, et al. Progressive multifocal leukoencephalopathy after natalizumab monotherapy. N Engl J Med, 2009;361(11):1081–1087.

16. Nieuwkamp DJ, Murk JL, Van Oosten BW, et al. PML in a patient without severe lymphocytopenia receiving dimethyl fumarate. N Engl J Med, 2015;372(15):1474–1476.

17. Perkins MR, Ryschkewitsch C, Liebner JC, et al. Changes in JC virus-specific T cell responses during natalizumab treatment and in natalizumab-associated progressive multifocal leukoencephalopathy. Plos Pathog, 2012;8(11):e1003014 [cit. 2017-11-12]. Dostupné na www: https://doi.org/10.1371/journal.ppat.1003014.

18. Vermersch P, Kappos L, Gold R, et al. Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy. Neurol, 2011;76(20):1697–1704.

19. Yousry TA, Pelletier D, Cadavid D, et al. Magnetic resonance imaging pattern in natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol, 2012;72(5):779–787.

20. Amend KL, Turnbull B, Foskett N, et al. Incidence of progressive multifocal leukoencephalopathy in patients without HIV. Neurol, 2010;75(15):1326–1332.

21. Power C, Brown Gladen JG, Halliday W, et al. AIDS and non AIDS – related PML association with distinct p53 polymorphism. Neurol, 2000;54(3):743–746.

22. Aotsuka Y, Uzawa A, Nishimura K, et al. Progressive multifocal leukoencephalopathy localized in the cerebellum and brainstem associated with idiopathic CD4+ T lymphocytopenia. Intern Med, 2016;55(12):1645–1647.

23. Pavlovic D, Patera AC, Nyberg F, et al. Progressive multifocal leukoencephalopathy: current treatment options and future perspectives. Ther Adv Neurol Disord, 2015;8(6):255–273.

24. Durali D, de Goer de Herve M-G, Gasnault J, et al. B cells and progressive multifocal leukoencephalopathy: search for the missing link. Front Immunol, 2015;6:241 [cit.2017-07-10]. Dostupné www: https://doi.org/10.3389/fimmu.2015.00241.

25. Epperla N, Medina-Flores R, Mazza JJ, et al. Mirtazapine and mefloquine therapy for non-AIDS-related progressive multifocal leukoencephalopathy. WMJ, 2014;113(6):242–245.

26. Tan CS, Dezube BJ, Bhargava P, et al. Detection of JC virus DNA and proteins in the bone marrow of HIV-positive and HIV-negative patients: implications for viral latency and neurotropic transformation. J Infect Dis, 2009;199(6):881–888.

27. Marshall LJ, Ferenczy MW, Daley EL, et al. Lymphocyte gene expression and JC virus noncoding control region sequences are linked with the risk of progressive multifocal leukoencephalopathy. J Virol, 2014;88(9):5177–5183.

28. Bellizzi A, Nardis C, Anzivino E, et al. Human polyomavirus JC reactivation and pathogenetic mechanisms of progressive multifocal leukoencephalopathy and cancer in the era of monoclonal antibody therapies. J Neurovirol, 2012;18(1):1–11.

29. White MK, Khalili K. Pathogenesis of progressive multifocal leukoencephalopathy-revisited. J Infect Dis, 2011; 203(5):578–586.

30. Jelcic I, Faigle W, et al. Immunology of progressive multifocal leukoencephalopathy. J Neurovirol, 2015;21(6):614–622.

31. Kurmann R, Weisstanner C, Kardas P, et al. Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine. J Neurovirol, 2015;21(6):694–701.

32. Marshall LJ, Dunham L, Major EO. Transcription factor Spi-B binds unique sequences present in the tandem repeat promote/enhancer of JC virus and supports viral activity. J Gen Virol, 2010;91(12):3042–3052.

33. Bonafoux D, Nanthakumar S, Bandarage UK, et al. Fragment-based discovery of dual JC virus and BK virus helicase inhibitors. J Med Chem, 2016; 59(15):7138–7151.

34. Randhawa P, Zeng G, Bueno M, et al. Inhibition of large T antigen ATPase activity as potential strategy to develop anti-polyomavirus JC drugs. Antiviral Res, 2014;0:113–119.

35. Seguin SP, Ireland AW, Gupta T, et al. A screen for modulators of large T antigen´s ATPase activity uncovers novel inhibitors of Simian Virus 40 and BK virus replication. Antiviral Res, 2012;96(1):70–81.

36. Beltrami S, Gordon J. Immune surveillance and response to JC virus infection and PML. J Neurovirol, 2014;20(2):137–149.

37. Sariyer IK, Merabova N, Patel PK, et al. Bag3-induced autophagy is associated with degradation of JCV oncoprotein, T-Ag. PLoS One, 2023;7:e45000 [cit. 2017-09-12]. Dostupné na www: https://doi.org/10.1371/journal.pone.0045000.

38. Hatchwell E. Is there a (host) genetic predisposition to progressive multifocal leukoencephalopathy? Front Immunol, 2015;6:216 [cit. 2017-10-12]. Dostupné na www: https://www.frontiersin.org/articles/10.3389/fimmu.2015.00216/full.

39. Mori I. Transolfactory neuroinvasion by viruses threatens the human brain. Acta virol, 2015;59(4):338–349.

40. Warnke C, Ramanujam R, Plavina T, et al. Changes to anti-JCV antibody levels in a Swedish national MS cohort. J Neurol Neurosurg Psychiatry, 2013;84(11):1199–1205.

41. Trbojevic M. Detection of oligoclonal Ig bands: clinical significance and trends in methodological improvement. eJIFCC, 2004;15 [cit. 2017-08-11]. Dostupné na www: http://www.ifcc.org/ejifcc/vol15no3/150309200413.htm.

42. Khanna N, Wolbers M, Mueller NJ, et al. JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy. J Virol, 2009;83(9):4404–4411.

43. Monaco MCG, Major EO. Immune system involvement in the pathogenesis of JC virus induced PML: what is learned from studies of patients with underlying diseases and therapies as risk factor. Front Immunol, 2015;6:159 [cit. 2017-08-11]. Dostupné na www: http://doi.org/10.3389/fimmu.2015.00159.

44. Du Pasquier RA, Clark KW, Smith PS, et al. JCV-specific cellular immune response correlates with a favorable clinical outcome in HIV-infected individuals with progressive multifocal leukoencephalopathy. J Neurovirol, 2001;7(4):318–322.

45. Seng R, Goujard C, Krastinova E, et al. Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy. AIDS, 2015;29(5):595–607.

46. Sokol J, Lisá L, Zeleňáková J, et al. Rituximab – associated progressive multifocal leukoencephalopathy. Vnitř Lék, 2017;63(1):60–64.

47. Lima MA, Berna-Cano F, Clifford DB, et al. Clinical outcome of long/term survivors of progressive multifocal leukoencephalopathy. J Neurol Neurosurg Psychiatry, 2010;81(11):1288–1291.

48. Černý R, Machala L. Neurologické komplikace HIV/AIDS. Praha: Karolinum; 2007.

49. Jelcic I, Combaluzier B, Jelcic I, et al. Prevention and therapy of JC polyomavirus-mediated progressive multifocal leukoencephalopathy – a realistic possibility? Swiss Med Wkly, 2017;147:w14520 [cit. 2017-05-09]. Dostupné na www: http://www.zora.uzh.ch/id/eprint/142365/1/Jelcic_et_al.pdf.

50. Aly L, Yousef S, Schippling S, et al. Central role of JC virus-specific CD4+ lymphocytes in progressive multi-focal leukoencephalopathy-immune reconstitution inflammatory syndrome. Brain, 2011;134:2687–2702.

51. Berger JR, Aksamit AJ, Clifford DB, et al. PML diagnostic criteria – consensus statement from the AAN Neuroinfectious Disease Section. Neurol, 2013;80(15):1430–1438.

52. Polsky B, Suh JS. Viral Infections. In Kuritzke DR, Eron JJ, Squires KE. InPractice HIV [on line]. Jointly Provided by USF Health and Clinical Care Opinions, LLC. 2014 [cit. 2017-11-09]. Dostupné na www: http://www.inpractice.com/Textbooks/HIV/Management_of_Specific_Disease_States/ch29_pt1_Viral/Chapter-Pages/Page-5.aspx.

53. Berger JR. The clinical features of PML. Cleve Clin J Med, 2011;78(S2):8–12.

54. Boster A, Hreha S, Berger JR, et al. Progressive multifocal leukoencephalopathy and relapsing – remitting multiple sclerosis; a comparative study. Arch Neurol, 2009;66(5):593–599.

55. Coyle P, Foley J, Fox E, et al. Best practice recommendations for the selection and management of patients with multiple sclerosis receiving natalizumab therapy. Mult Scler, 2009;15:26–36 [cit. 2017-10-10].

56. Lima MA, Drislane FW, Koralnik IJ. Seizures and their outcome in progressive multifocal leukoencephalopathy. Neurol, 2006;66(2):262–264.

57. O´Connor PW. Natalizumab risk stratification: role of two – step anti JCV antibody assay. Can J Neurol Sci, 2012;39(5):670–675.

58. Anzai Y. Infectious and demyelinating disease. Progressive multifocal leukoencephalopathy. In: Osborn AG, Salzman KL, Barkovich AJ. Diagnostic imaging brain. 2nd ed. Amirsys: Altona. 2010. p. 92–93.

59. Metz I, Radue EW, Oterino A, et al. Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis with natalizumab-associated progressive multifocal leukoencephalopathy. Acta Neuropathol, 2012;123(2):235–245.

60. Reuwer AQ, Heron M, van der Dussen D, et al. The clinical utility of JC virus antibody index measurements in the context of progressive multifocal leukoencephalopathy. Acta Neurol Scand, 2017; 136(S 201):37–44.

61. Salmen A, von Ahsen N, Trampe AK, et al. Longitudinal analyses of anti-JCV antibody index for risk assessment of progressive multifocal leukoencephalopathy. Mult Scler J Exp Transl Clin,2016;2:2055217316630008 [cit. 2017-10-10]. Dostupné na www: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433507/.

62. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. October 28, 2014 [on line]. Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV medicine Association of the Infectious Diseases Society of America [cit.2017-06-02]. Dostupné na www: https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-oi-prevention-and-treatment-guidelines/.

63. Polák P. Editoria on Sokol J, Lisá L, Zeleňáková J, et al. Rituximab – associated progressive multifocal leukoencephalopathy. Vnitř Lék, 2017;63(1):22–23.

64. Tan IL, McArthur JC, Clifford DB, et al. Immune reconstitution inflammatory syndrome in natalizumab-associated PML. Neurol, 2011;77(11):1061–1067.

65. Antoniol C, Jílek S, Schluep M, et al. Impairment of JCV-specific T-cell response by corticotherapy: effect on PML-IRIS management? Neurology, 2012;79(23):2258–2264.

66. Scarpazza C, Prosperini L, Mancinelli CR, et al. Is maraviroc useful in multiple sclerosis patients with natalizumab-related progressive multifocal leukoencephalopathy? J Neurol Sci, 2017; 378:233–237.

67. Himedan M, Camelo-Piragua S, Mills EA, et al. Pathologic findings of chronic PML-IRIS in a patient with prolonged PML survival following natalizumab treatment. J Investig Med High Impact Case Rep, 2017;5:2324709617734248 [cit. 2017-09-08]. Dostupné na www: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624358/.

68. Elphick GF, Querbes W, Jordan JA, et al. The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science, 2004;306(5700):1380–1383.

69. Trentalange A, Calcagno A, Ghisetti V, et al. Clearance of cerebrospinal fluid JCV DNA with mirtazapine in a patient with progressive multifocal leukoencephalopathy and sarcoidosis. Antivir Ther, 2016;21(7):633–635.

70. Cettomai D, McArthur JC. Mirtazapine use in human immunodeficiency virus-infected patients with progressive multifocal leukoencephalopathy. Arch Neurol, 2009;66(2):255–258.

71. Brickelmaier M, Lugovskoy A, Kartikeyan R, et al. Identification and characterization of mefloquine efficacy against JC virus in vitro. Antimicrob Agents Chemother, 2009;53(5):1840–1849.

72. Nukuzuma S, Kameoka M, Sugiura S, et al. Suppressive effect of PARP-1 inhibitor on JC virus replication in vitro. J Med Virol, 2013;85(1):132–137.

73. Kock K, Grube M, Jedlitschky G, et al. Expression of adenosine triphosphate-binding cassette (ABC) drug transporters in peripheral blood cells. Clin Pharmacokinet, 2007;46(6):449–470.

74. Barraud de Lagerie S, Comets E, Gautrand C, et al. Cerebral uptake of mefloquine enantiomers with and without the P-gp inhibitor elacridar (GF1210918) in mice. Br J Pharmacol, 2004;141(7):1214–1222.

75. Senarathna SM, Page-Sharp M, Crowe A. The interactions of P-glycoproteine with antimalarial drugs, including substrate affinity, inhibition and regulation. PloS One, 2016;11(4): e0152677 [cit. 2017-10-10]. Dostupné na www: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821601/.

76. Oga EF, Sekine S, Shitara Y, et al. Potential P-glycoprotein-mediated drug-drug interactions of antimalarial agents in caco-2 cells. Am J Trop Med Hyg, 2012;87(1):64–69.

77. Gofton TE, Al-Khotani A, O´Farrell B, et al. Mefloquine in the treatment of progressive multifocal leukoencephalopathy. J Neurol Neurosurg Psychiatry, 2011;82(4):452–455.

78. Moenster RP, Jett RA. Mirtazapine and mefloquine therapy for progressive multifocal leukoencephalopathy in a patient infected with human immunodeficiency virus. Am J Health Syst Pharm, 2012;69(6):496–498.

79. Clifford DB, Nath A, Cinque P, et al. A sudy of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes. J Neurovirol, 2013;19(4):351–358.

80. Khatri BO, Man S, Giovannoni G, et al. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function. Neurol, 2009;72(5):402–409.