title: Progressive multifocal leukoencephalopathy in a patient with common variable immunodeficiency and abnormal CD8+ T-cell subset distribution.
abstract: BACKGROUND
  Patients with primary hypogammaglobulinemia have been reported to have encephalopathy, but progressive multifocal leukoencephalopathy (PML) due to JC virus reactivation is a rare cause.
  
  
  OBJECTIVE
  To provide the clinical details and case discussion of a patient diagnosed as having common variable immunodeficiency (CVID) who has progressive neurodegenerative symptoms and was found to have PML and an abnormal CD8+ T-cell subset distribution.
  
  
  METHODS
  A detailed case report providing the patient's immunodeficiency history, diagnostic evaluation, and medical management and a review of related literature.
  
  
  RESULTS
  Before his neurodegenerative illness, the patient was found to have hypogammaglobulinemia, poor specific antibody responses, low circulating B-cell levels, and abnormal delayed-type hypersensitivity responses; there was no Bruton tyrosine kinase (BTK) mutation. The PML was diagnosed using brain biopsy and was confirmed using a DNA probe specific for JC virus. Peripheral blood flow cytometry at the time of PML diagnosis revealed an accumulation of naive CD8+ T cells (CD3+CD8+CD45RA+) and a deficiency of memory CD8+ T-cell subsets (CD3+CD8+CD45RA- or CD3+CD8+CD45RO+). Despite aggressive treatment with interleukin 2, interferon-gamma, and intravenous cidofovir, the patient died.
  
  
  CONCLUSIONS
  JC virus infection should be considered in the differential diagnosis of the patient with CVID and signs and symptoms of encephalopathy. The role of this patient's abnormal CD8' T-cell subset distribution in the development or control of this rare infection is worthy of consideration and has encouraged us to enumerate naive and memory CD4+ and CD8+ T-cell subsets in patients diagnosed as having CVID, even in the absence of neurodegenerative symptoms.
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Narula
authors.forename: David F
authors.initials: DF
authors.lastname: LaRosa
authors.forename: Malek
authors.initials: M
authors.lastname: Kamoun
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
authors.forename: Arnold I
authors.initials: AI
authors.lastname: Levinson
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017074:Common Variable Immunodeficiency / Q000150:complications* / Q000276:immunology; D006801:Humans; D007577:JC Virus / Q000302:isolation & purification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000209:etiology* / Q000276:immunology; D008297:Male; D014775:Virus Activation