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- Warnke, Clemens, et al.
(författare)
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Cerebrospinal Fluid JC Virus Antibody Index for Diagnosis of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
- 2014
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 76:6, s. 792-801
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AI(JCV)) in the diagnosis of natalizumab-associated PML.Methods: AI(JCV) was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AI(JCV) was calculated as published.Results:Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AI(JCV) > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AI(JCV) > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AI(JCV) > 1.5.Interpretation: Determination of the AI(JCV) could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML. Ann Neurol 2014;76:792-801
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| 2. |
- Warnke, Clemens, et al.
(författare)
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Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF
- 2015
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1036-1044
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Tidskriftsartikel (refereegranskat)abstract
- Background: Natalizumab for multiple sclerosis (MS) increases the risk of progressive multifocal leukoencephalopathy (PML). Objective: We aimed to assess the effect of natalizumab on cellular composition and functional B cell parameters including patients with natalizumab-associated PML (n=37). Methods: Cellular composition by flow cytometry, levels of immunoglobulin (Ig)G/IgM by immunonephelometry, and oligoclonal bands by isoelectric focusing were studied in blood and cerebrospinal fluid. Results: In MS patients treated with natalizumab without PML (n=59) the proportion of CD19+ B cells was higher in blood, but lower in cerebrospinal fluid compared with MS patients not treated with natalizumab (n=17). The CD4/CD8-ratio in cerebrospinal fluid was lower, and IgG and IgM levels as well as the IgG index dropped in longitudinal samples during natalizumab therapy. Oligoclonal bands persisted, but the total amount of the intrathecally produced IgG fraction, and the polyclonal intrathecal IgG reactivity to measles, rubella, and zoster declined. At the time of diagnosis of PML patients with natalizumab-associated PML had low total IgG levels in blood and cerebrospinal fluid. Conclusions: Natalizumab impacts B and T cell distribution and exerts an inhibitory effect on surrogates of B cell function in periphery and in cerebrospinal fluid, potentially contributing to the increased risk of developing PML.
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