Figure Pathogenesis of progressive multifocal leukoencephalopathy (PML)‏ Pathogenesis of progressive multifocal leukoencephalopathy (PML) Steps 1–3 show.

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Date of download: 5/30/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Natalizumab: Bench to Bedside and Beyond JAMA Neurol.

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Carrie M. Hersh, D.O., Robert Fox, M.D.

Copyright © 2009 American Medical Association. All rights reserved.

Figure 2 ALSFRS-R changes (A) Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) slope after 6 months of treatment without (left)

Figure 4. Brain imaging and neuropathologic demonstration of Epstein-Barr virus (EBV) encephalitis in patient PT-10 Brain imaging and neuropathologic demonstration.

Figure 3 Immunohistochemical analyses of positive and negative Epstein-Barr virus (EBV) control tissues using immunostaining Immunohistochemical analyses.

Figure 1 Coronal MRI images showing the evolution of white matter abnormality and atrophy of patient 1 Coronal MRI images showing the evolution of white.

Anti-integrin therapy in inflammatory bowel disease

Figure Brain MRI of the patient throughout the disease course(A) Brain MRI at the time of cerebral toxoplasmosis diagnosis (a) and after 1 month of toxoplasmosis.

Nat. Rev. Neurol. doi: /nrneurol

Figure 5 Treatment with fingolimod raises the activation threshold of monocytes in MS Peripheral blood mononuclear cells from 8 healthy donors, 7 patients.

Figure 3 JCV index changes in JCV+ patients

Figure Immune checkpoint inhibitor–induced encephalitis before and after treatment with natalizumab Immune checkpoint inhibitor–induced encephalitis before.

Figure 1 Neuromyelitis optica spectrum disorder (NMOSD) subgroups and patients with relapsing-remitting multiple sclerosis (RRMS) show different antibody.

Figure Nuclear Nrf2 expression after fumarate therapy A new left occipital fluid-attenuated inversion recovery hyperintense (A), T1 hypointense (B), and.

Figure 2 Elevated antibody reactivities against myelin and Epstein-Barr virus (EBV) peptides in relapsing-remitting multiple sclerosis (RRMS) and higher.

Figure 5 Increased frequency of parenchymal CD138- and LMP-1–positive cells in MS Increased frequency of parenchymal CD138- and LMP-1–positive cells in.

Figure 2 Neuropathology of PML lesions in a patient with MS treated with fingolimod Neuropathology of PML lesions in a patient with MS treated with fingolimod.

Figure 1 MOR103 sequential-dose trial flowchart of study population with multiple sclerosis aPatients received 2 doses of study drug before trial withdrawal.

Figure 1 8-Iso-PGF2α levels in CSF of patients with MS and controlsCSF 8-iso-prostaglandin F2α (8-iso-PGF2α) levels were estimated using an ELISA. (A)

Figure 2 7T MRI can differentiate between early PML and MS lesions Two different patterns of brain lesions were observed using 7T MRI: ring-enhancing lesions.

Figure 3 Punctate PML lesions visualized by highly resolving T2

Figure 2 Mean serum concentrations of BIIB033 vs time(A) Single ascending dose study and (B) multiple ascending dose study. Mean serum concentrations of.

Figure. Groups 1–3, patients tested, and test results (viral PCR and antibodies)‏ Groups 1–3, patients tested, and test results (viral PCR and antibodies)

Figure 2 JCV index JCV index (A) Fifty samples of natalizumab-treated patients with multiple sclerosis were assessed twice for their anti-JCV antibody.

Figure 3. Brain imaging and neuropathologic studies in patient PT-5 diagnosed with progressive multifocal leukoencephalopathy Brain imaging and neuropathologic.

Figure 1 Schematic overview of flow cytometry Schematic overview on the analysis of peripheral immune cells by flow cytometry. Schematic overview of flow.

Figure 1 Evolution of blood cell counts during 18-month treatment and follow-up (A) Mean white blood cell count, (B) mean lymphocyte count, (C) mean eosinophil.

Figure 5 Increased B cell-activating factor (BAFF) levels are shared between immunomodulatory treatments Increased B cell-activating factor (BAFF) levels.

Figure 1 JCV serostatus JCV serostatus (A) Serostatus of 1,921 natalizumab-treated patients with multiple sclerosis, with JCV− patients shown in black.

Figure 5 Pairwise correlations between selected patient-reported outcomes and performance tests in patients with MS (A) The number of pairwise correlations.

Figure 3 Longitudinal performance of 2 MS–cohabitant participant pairs on Ishihara color testing Both response speed and response accuracy are provided.

Figure 4 Shared and unique immune changes induced by multiple sclerosis (MS) immunomodulatory treatments Shared and unique immune changes induced by multiple.

Figure Postcontrast axial and coronal brain MRI in a patient with CLIPPERS treated with hydroxychloroquineT1-weighted spin echo post IV gadolinium contrast.

Figure 1 Annual trend in specimen type submitted as first sample for aquaporin-4 immunoglobulin G testing (serum only vs CSF only vs both) from 101,065.

Figure 2 Reduced frequency of central memory CD4 T cells in patients with PML Reduced frequency of central memory CD4 T cells (CD4Tcm) (p < ), naive.

Figure 6 Cellular composition after tissue dissociation

Figure 1 Examples illustrating gating strategy for fluorescence-activated cell sorting (FACS)‏ Examples illustrating gating strategy for fluorescence-activated.

Figure 2 Immunohistological detection of EBV latent and early lytic proteins in MS and control brains Immunohistological detection of EBV latent and early.

Figure 1 Evolution of MRI findings during interleukin (IL)–7 therapy

Figure 1. Radiologic and pathologic findings

Figure 3 Multiple sclerosis (MS) immunomodulatory treatments interferon-β (IFNB) and fingolimod (FTY720) result in global perturbation of the immune system.

Figure 1 Anti-Epstein-Barr virus nuclear antigen-1 IgG quartile antibody status differences in MRI measures Anti-Epstein-Barr virus nuclear antigen-1 IgG.

Figure 1 BG-12 treatment reduced total circulating B cells and had variable effects on memory B cells BG-12 treatment reduced total circulating B cells.

Figure 2 CD4+ T-cell subsets fluorescence-activated cell sorting analysis in peripheral blood mononuclear cells of patients with multiple sclerosis treated.

Figure 2 Pre- and posttreatment contrast-enhanced MRI of second toxoplasmosis lesion in case 1(A) Contrast-enhanced MRI demonstrated a second ring-enhancing.

Figure 1 CD52 expression on innate myeloid and lymphoid cell subsets

Figure Brain MRI findings before and during appearance of lymphoproliferative disorder and pathology findings of cerebellar lesion Brain MRI findings before.

Figure 2 Repopulation of CD19+ cells in low and high BSA patients and calculation of the BSA Repopulation of CD19+ cells in low and high BSA patients and.

Figure 2 Evolution of blood cell counts during interleukin (IL)–7 therapy Evolution of blood cell counts during interleukin (IL)–7 therapy The leukocyte.

Figure Avidity of IgG specific for influenza A and B following flu vaccinationAvidity of immunoglobulin (Ig) G specific for influenza A and B before and.

Figure 2 Natalizumab increases expression of proinflammatory genes and cytokines by CD49d+ memory CD4 cells Natalizumab increases expression of proinflammatory.

Figure 3 Effect of IVIg on endogenous relative concentration (in mAb equivalents) of JCV AbSix patients shown in this figure have had John Cunningham virus.

Figure 2 CD56bright natural killer (NK) cell counts in daclizumab high-yield process (DAC HYP)-treated patientsData are medians with 25th and 75th percentiles.

Figure 1 Peripheral blood lymphocyte counts during dose titrationB-lymphocyte (CD19+; A) and total lymphocyte (CD45+; B) counts (cells/µL) in peripheral.

Figure 1 Classical pathway and lectin pathway activity in patients with multifocal motor neuropathy and controls Classical pathway (CP) activity (A) and.

Figure 1 Detailed overview of treatment course and paraclinical findings Maximum intensity projection maps of supratentorial inversion recovery images.

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Figure 6 Multiple target epitopes exist in the N-terminal domains of Caspr2 (A) Multidomain deletion constructs of Caspr2 were generated to determine which.

Figure 2 Cell-based assay demonstrating differential binding of AChR antibodies to the adult and fetal receptorsThe fetal (gamma subunit specific) and.

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Figure 2 MRIs (cases 2 and 3)‏

Figure 3 Alemtuzumab-induced changes in monocytes

Figure 4 Patient 3 MRI evolution over time

Figure 2 Time from incident ADS event to MS diagnosis

Figure 1 Numbers/seropositivity rates of IVIg-naive and IVIg-exposed STRATIFY-2 enrollees* = % of enrollment samples, ** = date of IVIg and/or concentration.

Figure 2. Percentage of CD16− monocytes in the blood is reduced during disease progression Percentage of CD16− monocytes in the blood is reduced during.

Figure (A and B) Effect of canakinumab in muscle strength measured in each patient as mean bilateral GF (A) and TMS (B) during the mean study period of.

Figure 4 Longitudinal analysis of peripheral immune cell composition Frequency of naive, central memory (Tcm), and effector memory (Tem) CD4 T cells over.

Presentation transcript:

Figure Pathogenesis of progressive multifocal leukoencephalopathy (PML)‏ Pathogenesis of progressive multifocal leukoencephalopathy (PML) Steps 1–3 show initiation of JC virus (JCV) infection, and establish latency in kidney that can become persistent in lymphoid organs, notably the bone marrow, in which the viral regulatory region sequences become rearranged from the nonvirulent to a neurovirulent or PML variant. Steps 4–6 involve the biological effects of natalizumab treatment over time, forcing migration of CD 34+ and pre-B cells into the circulation since it prevents homing of these cells in the marrow due to blocking of binding to cell adhesion molecules. At these steps, natalizumab is associated with temporal gene regulation of a number of factors including those that augment JCV replication that may account for high incidence of PML in patients with multiple sclerosis treated with natalizumab for 24 doses or more. Steps 7–10 show progression of JCV to the brain and establishment of PML. The authors thank David Carter, In Tune Communications, Canada, for assembly of the figure. EBV = Epstein-Barr virus. Eugene O. Major, and Avindra Nath Neurol Neuroimmunol Neuroinflamm 2016;3:e235 © 2016 American Academy of Neurology