title: Immunological and clinical consequences of treating a patient with natalizumab.
abstract: BACKGROUND
  Long-term therapy with natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML).
  
  
  OBJECTIVE
  We present a patient study through therapy, the diagnosis of PML (after 29 infusions), plasma exchange (PE) and development of immune reconstitution inflammatory syndrome (IRIS).
  
  
  METHODS
  Routine diagnostics, magnetic resonance imaging (MRI), immunological status (flow cytometry, T-cell migration assays and T-cell repertoire analysis), and brain biopsy with immunohistological analysis.
  
  
  RESULTS
  CD49d decreased after 12 months of treatment. At PML diagnosis, CD49d expression and migratory capacity of T cells was low and peripheral T-cell receptor (TCR) complexity showed severe perturbations. The distribution of peripheral monocytes changed from CCR5+ to CCR7+. After PE some changes reverted: CD49d increased and overshot earliest levels, migratory capacities of T cells recovered and peripheral TCR complexity increased. With no clinical, routine laboratory or cerebrospinal fluid (CSF) changes, MRI 2 months after PE demonstrated progressive lesion development. Brain histopathology confirmed the presence of infiltrates indicative of IRIS without clinical signs, immunologically accompanied by CCR7/CCR5 recovery of peripheral monocytes.
  
  
  CONCLUSIONS
  Natalizumab-associated immunological changes accompanying PML were reversible after PE; IRIS can occur very late, remain asymptomatic and be elusive to CSF analysis. Our study may provide insights into the changes under treatment with natalizumab associated with JC virus control.
authors: Department of Neurology-Inflammatory Disorders of the Nervous System and Neurooncology, University of Münster, Münster, Germany.
authors: Nicholas
authors: N
authors: Schwab
authors: Karin G
authors: KG
authors: Höhn
authors: Tilman
authors: T
authors: Schneider-Hohendorf
authors: Imke
authors: I
authors: Metz
authors: Max-Philipp
authors: MP
authors: Stenner
authors: Samantha
authors: S
authors: Jilek
authors: Renaud A
authors: RA
authors: Du Pasquier
authors: Ralf
authors: R
authors: Gold
authors: Sven G
authors: SG
authors: Meuth
authors: Richard M
authors: RM
authors: Ransohoff
authors: Wolfgang
authors: W
authors: Brück
authors: Heinz
authors: H
authors: Wiendl
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000276:immunology / Q000473:pathology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000276:immunology; D007577:JC Virus / Q000276:immunology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D000069442:Natalizumab; D010951:Plasma Exchange; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab