Analysis of John Cunningham Virus DNA in Immunosuppressed Patients

Year 2023, Volume: 12 Issue: 3, 1124 - 1130, 26.09.2023

Füsun Kırca , Bedia Dinç

https://doi.org/10.37989/gumussagbil.1320057

Abstract

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by John Cunningham Virus (JCV). JCV is rarely pathogenic in immunocompetent individuals but can reactivate in immunosuppressed patients and cause PML. This study aimed to analyze JCV DNA in immunosuppressed patients by quantitative real-time polymerase chain reaction (RT-PCR) and evaluate diagnostic performances of viral load and sample types in PML. A total of 142 JCV RT-PCR sample results of 115 patients sent to Molecular Microbiology Laboratory of the Ankara Bilkent City Hospital between March-2019 and May-2023 for diagnosis of JCV were retrospectively analysed. After nucleic acid isolation, amplification was performed quantitatively by RT-PCR on the Rotor-Gene Q device using the RealStar® JCV PCR Kit 1.0. JCV DNA was found positive in 11% of patients and 4 patients were diagnosed with PML by clinical and radiologic findings. CSF viral load levels of 3 patients with PML were found 104, 104 and 102 copies/ml, and the plasma viral load of the other patient was initially found 101 copies/ml, which increased to 102 in consecutive examinations. The plasma viral load of patients who were not diagnosed with PML was 101 copies/ml. Early diagnosis of PML is important for treatment planning. The detection of JCV DNA in CSF samples is considered highly sensitive and specific for diagnosis. An increase in viral load in consecutive plasma samples may also be valuable in the diagnosis of PML in cases where CSF cannot be obtained.

Keywords

CV, JCV DNA, PML, Progressive multifocal leukoencephalopathy

İmmünsuprese Hastalarda John Cunningham Virüs DNA Analizi

Abstract

Progresif multifokal lökoensefalopati (PML), John Cunningham Virüsünün (JCV) etken olduğu merkezi sinir sisteminin demiyelinizan bir hastalığıdır. İmmünkompetan bireylerde JCV nadiren patojeniktir, ancak immünsuprese hastalarda reaktive olarak PML’ye neden olabilir. Bu çalışmanın amacı, JCV enfeksiyonu için risk grubunda olan immünsuprese hastalarda JCV DNA’sının kantitatif gerçek zamanlı polimeraz zincir reksiyonu (RT-PCR) ile analizi ve PML hastalığında viral yük ve örnek tiplerinin tanı koymadaki performansının değerlendirilmesidir Mart 2019-Mayıs 2023 tarihleri arasında Ankara Bilkent Şehir Hastanesi Moleküler Mikrobiyoloji Laboratuvarına JCV tanısı için gönderilen, 115 hastaya ait toplam 142 örneğin JCV RT-PCR sonuçları retrospektif olarak değerlendirilmiştir. Klinik örneklerde nükleik asit izolasyonundan sonra amplifikasyon, RealStar® JCV PCR Kit 1.0 kullanılarak Rotor-Gene Q cihazında kantitatif olarak RT- PCR yöntemi ile çalışılmıştır. İncelenen hastaların %11’inde JCV DNA pozitif bulunmuş ve bunlardan 4 hasta klinik ve radyolojik bulguların desteklediği PML tanısı almıştır. PML tanısı almış 3 hastanın viral yük düzeyleri BOS’ta 104, 104 ve102 kopya/ml, diğer hastanın viral yük düzeyi plazmada önce 101 kopya/ml bulunmuş, ancak ardışık incelemede 102 kopya/ml’ye artış gösterdiği tespit edilmiştir. PML tanısı almayan hastaların plazmalarında viral yük ise 101 kopya/ml bulunmuştur. PML’nin erken tanısı, tedavinin planlanması açısından önem taşımaktadır. BOS örneğinde JCV DNA tespiti tanı için oldukça hassas ve spesifik olarak kabul edilmektedir. Bu çalışmada, BOS’un alınamadığı durumlarda ardışık çalışılan plazma örneklerinde virüs yükünde artış bulunmasının tanıda değerli olabileceği sonucuna varılmıştır.

Keywords

JCV, JCV DNA, PML, Progresif multifokal lökoensefalopati

References

• 1. Abrão, C.O, Silva, L.R.M.D, Souza, L.C.S, Bisso, N.M, Turchi, M.D. and Guilarde, A.O. (2020). “AIDS-Related Progressive Multifocal Leukoencephalopathy”. Revista da Sociedade Brasileira de Medicina Tropical, 54, e02522020. https://doi.org/10.1590/0037-8682-0252-2020.
• 2. Cortese, I, Reich, D.S and Nath, A. (2021). “Progressive Multifocal Leukoencephalopathy and the Spectrum of JC Virus-Related Disease”. Nature Reviews Neurology, 17 (1), 37–51. https://doi.org/10.1038/s41582-020-00427-y.
• 3. White, M.K, Sariyer, I.K, Gordon, J, Delbue, S, Pietropaolo, V, Berger, J.R. and Khalili, K. (2016). “Diagnostic Assays for Polyomavirus JC and Progressive Multifocal Leukoencephalopathy”. Reviews in Medical Virology, 26 (2), 102–114. https://doi.org/10.1002/rmv.1866.
• 4. Zheng, H.Y, Kitamura, T, Takasaka, T, Chen, Q. and Yogo, Y. (2004). “Unambiguous İdentification of JC Polyomavirus Strains Transmitted From Parents to Children”. Archives of Virology, 149 (2), 261–273. https://doi.org/10.1007/s00705-003-0214-6.
• 5. Adang, L. and Berger, J. (2015). “Progressive Multifocal Leukoencephalopathy”. F1000Research, 4, 1424. https://doi.org/10.12688/f1000research.7071.1.
• 6. Demirbuğa, A, Kaba, O, Törün, S.H, Yıldız, E.P, Yücel, E. and Somer, A. (2021). “Progressive Multifocal Leukoencephalopathy in Children with Primary and Secondary Immune Deficiency”. Pediatric Allergy İmmunology and Pulmonology, 34 (3), 109–111. https://doi.org/10.1089/ped.2020.1330.
• 7. Nakamichi, K, Miura, Y, Shimokawa, T, Takahashi, K, Suzuki, T, Funata, N, Harada, M, Mori, K, Sanjo, N, Yukitake, M, Takahashi, K, Hamaguchi, T, Izaki, S, Oji, S, Nakahara, J, Ae, R, Kosami, K, Nukuzuma, S, Nakamura, Y, Nomura, K, Kishida, S, Mizusawa, H, Yamada M, Takao M, Ebihara H. and Saijo, M. (2023). “Nationwide Laboratory Surveillance of Progressive Multifocal Leukoencephalopathy in Japan: Fiscal Years 2011-2020”. Viruses, 15 (4), 968. https://doi.org/10.3390/v15040968.
• 8. Tan, C.S. and Koralnik, I.J. (2010). “Progressive Multifocal Leukoencephalopathy and Other Disorders Caused by JC Virus: Clinical Features and Pathogenesis”. The Lancet Neurology, 9 (4), 425–437. https://doi.org/10.1016/S1474-4422(10)70040-5.
• 9. Ferenczy, M.W, Marshall, L.J, Nelson, C.D, Atwood, W.J, Nath, A, Khalili, K. and Major, E.O. (2012). “Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-İnduced Demyelinating Disease of the Human Brain”. Clinical Microbiology Reviews, 25 (3), 471–506. https://doi.org/10.1128/CMR.05031-11.
• 10. Ferretti, F, Bestetti, A, Yiannoutsos, C.T, Musick, B.S, Gerevini, S, Passeri, L, Bossolasco, S, Boschini, A, Franciotta, D, Lazzarin, A. and Cinque, P. (2018). “Diagnostic and Prognostic Value of JC Virus DNA in Plasma in Progressive Multifocal Leukoencephalopathy”. Clinical İnfectious Diseases: an official publication of the Infectious Diseases Society of America, 67 (1), 65–72. https://doi.org/10.1093/cid/ciy030.
• 11. Çolak M, Altay Koçak A, Erten Y, Özkurt Z, Özkan S, Pınar A. ve Bozdayı G. (2015). “İmmünsüprese Hastalarda Gerçek Zamanlı Polimeraz Zincir Reaksiyonu (Real-Time PCR) ile BKV ve JCV DNA Pozitifliğinin Araştırılması”. Türk Mikrobiyoloji Cemiyeti Dergisi, 45 (1), 12–21.
• 12. Çolak M, Altay Koçak A, Aydın Kaynar L, Muftah H, Özkurt ZN, Yeğin ZA. ve Bozdayı G. (2020). “Hematopoietik Kök Hücre Nakli Olmuş Hastalarda JC virüs Pozitifliğinin Gerçek-Zamanlı Polimeraz Zincir Reaksiyonu ile Araştırılması”. Flora Dergisi, 25 (1), 40-6. DOI:10.5578/flora.68466.
• 13. Rota, S, Fidan, K, Bozdayı, G, Dalgıç, A, Fidan, I, Sucak, G. ve Müderris, T. (2011). “Yüksek Risk Altındaki Hastaların Klinik Örneklerinde BK ve JC Virus DNA Pozitifliğinin Gerçek Zamanlı Polimeraz Zincir Reaksiyonu ile Araştırılması”. Mikrobiyoloji Bulteni, 45 (2), 280–287.
• 14. Berger, J.R, Aksamit, A.J, Clifford, D.B, Davis, L, Koralnik, I.J, Sejvar, J.J, Bartt, R, Major, E.O. and Nath, A. (2013). “PML Diagnostic Criteria: Consensus Statement from the AAN Neuroinfectious Disease Section”. Neurology, 80 (15), 1430–1438. https://doi.org/10.1212/WNL.0b013e31828c2fa1.
• 15. Swinnen, B, Saegeman, V, Beuselinck, K, Wouters, A, Cypers, G, Meyfroidt, G. and Schrooten, M. (2019). “Predictive Value of JC Virus PCR in Cerebrospinal Fluid in the Diagnosis of PML”. Diagnostic Microbiology and İnfectious Disease, 95 (3), 114859. https://doi.org/10.1016/j.diagmicrobio.2019.06.011.
• 16. Cook, L. (2016). “Polyomaviruses”. Microbiology Spectrum, 4 (4). https://doi.org/10.1128/microbiolspec.DMIH2-0010-2015.
• 17. Iannetta, M, Zingaropoli, M.A, D'Abramo, A, Oliva, A, Mastroianni, C.M, Vullo, V. and Ciardi, M.R. (2016). “HIV-Associated Progressive Multifocal Leukoencephalopathy: Current Perspectives”. Neurobehavioral HIV Medicine, 7, 43–52. https://doi.org/10.2147/NBHIV.S107941.
• 18. Koralnik, I.J, Boden, D, Mai, V.X, Lord, C.I. and Letvin, N.L. (1999). “JC virus DNA Load in Patients With and Without Progressive Multifocal Leukoencephalopathy”. Neurology, 52 (2), 253–260. https://doi.org/10.1212/wnl.52.2.253.
• 19. Dubois, V, Dutronc, H, Lafon, M.E, Poinsot, V, Pellegrin, J.L, Ragnaud, J.M, Ferrer, A.M. and Fleury, H.J. (1997). “Latency and Reactivation of JC Virus in Peripheral Blood of Human Immunodeficiency Virus Type 1-Infected Patients”. Journal of Clinical Microbiology, 35 (9), 2288–2292. https://doi.org/10.1128/jcm.35.9.2288-2292.1997.