Progressive Multifocal Leukoencephalopathy in Primary Immunodeficiencies

J Clin Immunol. 2019 Jan;39(1):55-64. doi: 10.1007/s10875-018-0578-8. Epub 2018 Dec 14.


Purpose: Progressive multifocal leukoencephalopathy (PML) is a rare but severe demyelinating disease caused by the polyomavirus JC (JCV) in immunocompromised patients. We report a series of patients with primary immune deficiencies (PIDs) who developed PML.

Methods: Retrospective observational study including PID patients with PML. Clinical, immunological, imaging features, and outcome are provided for each patient.

Results: Eleven unrelated patients with PIDs developed PML. PIDs were characterized by a wide range of syndromic or genetically defined defects, mostly with combined B and T cell impairment. Genetic diagnosis was made in 7 patients. Before the development of PML, 10 patients had recurrent infections, 7 had autoimmune and/or inflammatory manifestations, and 3 had a history of malignancies. Immunologic investigations showed CD4+ lymphopenia (median 265, range 50-344) in all cases. Six patients received immunosuppressive therapy in the year before PML onset, including prolonged steroid therapy in 3 cases, rituximab in 5 cases, anti-TNF-α therapy, and azathioprine in 1 case each. Despite various treatments, all but 1 patient died after a median of 8 months following PML diagnosis.

Conclusion: PML is a rare but fatal complication of PIDs. Many cases are secondary to immunosuppressive therapy warranting careful evaluation before initiation subsequent immunosuppression during PIDs.

Keywords: Progressive multifocal leukoencephalopathy; combined immunodeficiencies; immunosuppressive therapy; polyomavirus JC; primary immunodeficiencies.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Azathioprine / therapeutic use
  • B-Lymphocytes / immunology
  • Female
  • Humans
  • Immunologic Deficiency Syndromes / complications*
  • Immunologic Deficiency Syndromes / immunology*
  • Immunotherapy / methods
  • JC Virus / immunology
  • Leukoencephalopathy, Progressive Multifocal / etiology*
  • Leukoencephalopathy, Progressive Multifocal / immunology*
  • Leukoencephalopathy, Progressive Multifocal / therapy
  • Lymphopenia / immunology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Rituximab / therapeutic use
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Young Adult


  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Azathioprine