ImmunoWELL JCV IgG assay as a novel tool for progressive multifocal leukoencephalopathy risk assessment in patients with multiple sclerosis Review article
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Published:
Jun 30, 2026
Keywords:
multiple sclerosis, progressive multifocal leukoencephalopathy, John Cunningham virus, anti-JCV antibodies, JCV index
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Abstract
With the increasing use of high-efficacy therapies in the treatment of multiple sclerosis, monitoring treatment safety has become increasingly important, particularly with regard to the risk of progressive multifocal leukoencephalopathy (PML) associated with natalizumab therapy. Assessment of antibodies against the John Cunningham virus (JCV) remains a key component of PML risk stratification. This article reviews current standards of JCV monitoring and discusses the role of the novel ImmunoWELL JCV IgG assay in the assessment of PML risk. Available evidence indicates that the ImmunoWELL JCV assay demonstrates high sensitivity and a high negative predictive value; however, it more frequently classifies patients into higher-risk categories than the previously established STRATIFY JCV assay. Although discrepancies between the two methods are mainly observed within the low and intermediate JCV index ranges, interpretation of ImmunoWELL JCV results requires caution, as current PML risk prediction models were developed using data generated with the STRATIFY JCV assay. The ImmunoWELL JCV assay represents a valuable tool for supporting safety monitoring in natalizumab-treated patients, but its results should be interpreted within the broader clinical context, taking into account individual patient characteristics and risk factors.
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References
1. Amato MP. Updated EAN-ECTRIMS guideline on pharmacological MS treatment. Conference Paper. EAN 2022, Aug 2022. https://doi.org/10.55788/b71ff3dc .
2. Serwis Edukacyjny PTN. Stanowisko polskich ekspertów klinicznych w sprawie miejsca wysoko efektywnych terapii w modelu leczenia stwardnienia rozsianego .
3. Statystyki NFZ .
4. Statystyki NFZ .
5. Rindi LV, Zaçe D, Braccialarghe N et al. Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis. Drug Saf. 2024; 47(4): 333-54. https://doi.org/10.1007/s40264-023-01383-4.
6. Joly M, Conte C, Cazanave C et al. Progressive multifocal leukoencephalopathy: epidemiology and spectrum of predisposing conditions. Brain. 2023; 146(1): 349-58. https://doi.org/10.1093/brain/awac237.
7. Gómez-Cibeira E, Ivanovic-Barbeito Y, Gutiérrez-Martínez E et al. Eculizumab-related progressive multifocal leukoencephalopathy. Neurology. 2016; 86(4): 399-400. https://doi.org/10.1212/WNL.0000000000002312.
8. Berger JR, Cree BA, Greenberg B et al. Progressive multifocal leukoencephalopathy after fingolimod treatment. Neurology. 2018; 90: E1815-21.
9. Newton P, Aldridge RD, Lessells AM et al. Progressive multifocal leukoencephalopathy complicating systemic lupus erythematosus. Arthritis Rheum. 1986; 29(3): 337-43. https://doi.org/10.1002/art.1780290305.
10. Pavlovic AM, Bonaci-Nikolic B, Kozic D et al. Progressive multifocal leukoencephalopathy associated with mycophenolate mofetil treatment in a woman with lupus and CD4+ T-lymphocyte deficiency. Lupus. 2012; 21(1): 100-2. https://doi.org/10.1177/0961203311416693.
11. Patel A, Sul J, Gordon ML et al. Progressive Multifocal Leukoencephalopathy in a Patient With Progressive Multiple Sclerosis Treated With Ocrelizumab Monotherapy. JAMA Neurol. 2021; 78(6): 736-40. https://doi.org/10.1001/jamaneurol.2021.0627.
12. Raisch DW, Rafi JA, Chen C et al. Detection of cases of progressive multifocal leukoencephalopathy associated with new biologicals and targeted cancer therapies from the FDA’s adverse event reporting system. Expert Opin Drug Saf. 2016; 15(8): 1003-11. https://doi.org/10.1080/14740338.2016.1198775.
13. Sriwastava S, Chaudhary D, Srivastava S et al. Progressive multifocal leukoencephalopathy and sphingosine 1-phosphate receptor modulators used in multiple sclerosis: an updated review of literature. J Neurol. 2022; 269(3): 1678-87. https://doi.org/10.1007/s00415-021-10910-1.
14. Carson KR, Evens AM, Richey EA et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood. 2009; 113(20): 4834-40. https://doi.org/10.1182/blood-2008-10-186999.
15. Weber T, Trebst C, Frye S et al. Analysis of the systemic and intrathecal humoral immune response in progressive multifocal leukoencephalopathy. J Infect Dis. 1997; 176(1): 250-4. https://doi.org/10.1086/514032.
16. Kartau M, Sipilä JO, Auvinen E et al. Progressive Multifocal Leukoencephalopathy: Current Insights. Degener Neurol Neuromuscul Dis. 2019; 9: 109-21. https://doi.org/10.2147/DNND.S203405.
17. Polman CH, O’Connor PW, Havrdova E et al.; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006; 354(9): 899-910. https://doi.org/10.1056/NEJMoa044397.
18. Dwyer CM, Jokubaitis VG, Stankovich J et al. High rates of JCV seroconversion in a large international cohort of natalizumab-treated patients. Ther Adv Neurol Disord. 2021; 14: 1756286421998915. https://doi.org/10.1177/1756286421998915.
19. Narodowy Fundusz Zdrowia. Załącznik B.29. Leczenie chorych na stwardnienie rozsiane (ICD-10: G35). 2025.
20. Inojosa H, Kather A, Akgün K et al. Challenges and implications of anti-JCV antibody serology variability among different assays in natalizumab treatment: A call for standardization and transparency in clinical practice. Mult Scler. 2025; 31(3): 376-7. https://doi.org/10.1177/13524585241300972.
21. Gelissen LMY, Wijburg MT, Strijbis EMM et al. Accuracy of New John Cunningham Virus Antibody Assay in Natalizumab-Treated Patients With Multiple Sclerosis. JAMA Neurol. 2025; 82(5): 523-524. https://doi.org/10.1001/jamaneurol.2025.0337.
22. Adler F, Andersen M, Bartl T et al. A new assay for detection of anti-JCV antibodies to support risk stratification and monitoring for progressive multifocal leukoencephalopathy in patients considering or in treatment with natalizumab. Poster presented at: 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); 2024 Sep 18–20; Copenhagen, Denmark. Poster P1836.
23. Varley J, Beyrouti R, Nicholas R et al. A comparison of JC virus assay performance provided with originator and biosimilar natalizumab. Mult Scler. 2025; 31(7): 882-5. https://doi.org/10.1177/13524585251346652.
24. Vukusic S, Hubben F, Gavoille A et al. Beyond the switch to the biosimilar of natalizumab: What is the impact of changing the JCV test? Mult Scler. 2025; 31(7): 877-81. https://doi.org/10.1177/13524585251322683.
25. Chisari CG, Crimì P, Spampinato G et al. Threshold-Dependent Discordance Between STRATIFY JCV™ and IMMUNOWELL™ Assays in Relapsing Multiple Sclerosis. Neurol Ther. 2026; 15(3): 1375-86. https://doi.org/10.1007/s40120-026-00937-9.
26. Esmael A, Schelcher C, Arani R et al. First-year multinational cohort data of the ImmunoWELL JCV test in natalizumab PML risk monitoring: descriptive analysis. Poster presented at: 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); 2025 Sep 24–26; Barcelona, Spain. Poster P2012.
27. Dobson R, Arun T, Varley J et al. Approach to JCV testing with natalizumab biosimilar: a UK consensus statement. Mult Scler Relat Disord. 2025; 100: 106541. https://doi.org/10.1016/j.msard.2025.106541.
2. Serwis Edukacyjny PTN. Stanowisko polskich ekspertów klinicznych w sprawie miejsca wysoko efektywnych terapii w modelu leczenia stwardnienia rozsianego .
3. Statystyki NFZ .
4. Statystyki NFZ .
5. Rindi LV, Zaçe D, Braccialarghe N et al. Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis. Drug Saf. 2024; 47(4): 333-54. https://doi.org/10.1007/s40264-023-01383-4.
6. Joly M, Conte C, Cazanave C et al. Progressive multifocal leukoencephalopathy: epidemiology and spectrum of predisposing conditions. Brain. 2023; 146(1): 349-58. https://doi.org/10.1093/brain/awac237.
7. Gómez-Cibeira E, Ivanovic-Barbeito Y, Gutiérrez-Martínez E et al. Eculizumab-related progressive multifocal leukoencephalopathy. Neurology. 2016; 86(4): 399-400. https://doi.org/10.1212/WNL.0000000000002312.
8. Berger JR, Cree BA, Greenberg B et al. Progressive multifocal leukoencephalopathy after fingolimod treatment. Neurology. 2018; 90: E1815-21.
9. Newton P, Aldridge RD, Lessells AM et al. Progressive multifocal leukoencephalopathy complicating systemic lupus erythematosus. Arthritis Rheum. 1986; 29(3): 337-43. https://doi.org/10.1002/art.1780290305.
10. Pavlovic AM, Bonaci-Nikolic B, Kozic D et al. Progressive multifocal leukoencephalopathy associated with mycophenolate mofetil treatment in a woman with lupus and CD4+ T-lymphocyte deficiency. Lupus. 2012; 21(1): 100-2. https://doi.org/10.1177/0961203311416693.
11. Patel A, Sul J, Gordon ML et al. Progressive Multifocal Leukoencephalopathy in a Patient With Progressive Multiple Sclerosis Treated With Ocrelizumab Monotherapy. JAMA Neurol. 2021; 78(6): 736-40. https://doi.org/10.1001/jamaneurol.2021.0627.
12. Raisch DW, Rafi JA, Chen C et al. Detection of cases of progressive multifocal leukoencephalopathy associated with new biologicals and targeted cancer therapies from the FDA’s adverse event reporting system. Expert Opin Drug Saf. 2016; 15(8): 1003-11. https://doi.org/10.1080/14740338.2016.1198775.
13. Sriwastava S, Chaudhary D, Srivastava S et al. Progressive multifocal leukoencephalopathy and sphingosine 1-phosphate receptor modulators used in multiple sclerosis: an updated review of literature. J Neurol. 2022; 269(3): 1678-87. https://doi.org/10.1007/s00415-021-10910-1.
14. Carson KR, Evens AM, Richey EA et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood. 2009; 113(20): 4834-40. https://doi.org/10.1182/blood-2008-10-186999.
15. Weber T, Trebst C, Frye S et al. Analysis of the systemic and intrathecal humoral immune response in progressive multifocal leukoencephalopathy. J Infect Dis. 1997; 176(1): 250-4. https://doi.org/10.1086/514032.
16. Kartau M, Sipilä JO, Auvinen E et al. Progressive Multifocal Leukoencephalopathy: Current Insights. Degener Neurol Neuromuscul Dis. 2019; 9: 109-21. https://doi.org/10.2147/DNND.S203405.
17. Polman CH, O’Connor PW, Havrdova E et al.; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006; 354(9): 899-910. https://doi.org/10.1056/NEJMoa044397.
18. Dwyer CM, Jokubaitis VG, Stankovich J et al. High rates of JCV seroconversion in a large international cohort of natalizumab-treated patients. Ther Adv Neurol Disord. 2021; 14: 1756286421998915. https://doi.org/10.1177/1756286421998915.
19. Narodowy Fundusz Zdrowia. Załącznik B.29. Leczenie chorych na stwardnienie rozsiane (ICD-10: G35). 2025.
20. Inojosa H, Kather A, Akgün K et al. Challenges and implications of anti-JCV antibody serology variability among different assays in natalizumab treatment: A call for standardization and transparency in clinical practice. Mult Scler. 2025; 31(3): 376-7. https://doi.org/10.1177/13524585241300972.
21. Gelissen LMY, Wijburg MT, Strijbis EMM et al. Accuracy of New John Cunningham Virus Antibody Assay in Natalizumab-Treated Patients With Multiple Sclerosis. JAMA Neurol. 2025; 82(5): 523-524. https://doi.org/10.1001/jamaneurol.2025.0337.
22. Adler F, Andersen M, Bartl T et al. A new assay for detection of anti-JCV antibodies to support risk stratification and monitoring for progressive multifocal leukoencephalopathy in patients considering or in treatment with natalizumab. Poster presented at: 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); 2024 Sep 18–20; Copenhagen, Denmark. Poster P1836.
23. Varley J, Beyrouti R, Nicholas R et al. A comparison of JC virus assay performance provided with originator and biosimilar natalizumab. Mult Scler. 2025; 31(7): 882-5. https://doi.org/10.1177/13524585251346652.
24. Vukusic S, Hubben F, Gavoille A et al. Beyond the switch to the biosimilar of natalizumab: What is the impact of changing the JCV test? Mult Scler. 2025; 31(7): 877-81. https://doi.org/10.1177/13524585251322683.
25. Chisari CG, Crimì P, Spampinato G et al. Threshold-Dependent Discordance Between STRATIFY JCV™ and IMMUNOWELL™ Assays in Relapsing Multiple Sclerosis. Neurol Ther. 2026; 15(3): 1375-86. https://doi.org/10.1007/s40120-026-00937-9.
26. Esmael A, Schelcher C, Arani R et al. First-year multinational cohort data of the ImmunoWELL JCV test in natalizumab PML risk monitoring: descriptive analysis. Poster presented at: 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); 2025 Sep 24–26; Barcelona, Spain. Poster P2012.
27. Dobson R, Arun T, Varley J et al. Approach to JCV testing with natalizumab biosimilar: a UK consensus statement. Mult Scler Relat Disord. 2025; 100: 106541. https://doi.org/10.1016/j.msard.2025.106541.