No interferon-beta antibodies in natalizumab-treated multiple sclerosis patients with progressive multifocal leukoencephalopathy

J Neurol Sci. 2026 Jul 15:486:125947. doi: 10.1016/j.jns.2026.125947. Epub 2026 Apr 28.

Abstract

Background: Interferon beta therapy (IFN-β) can induce production of antibodies (NAbs) that may neutralize both therapeutic IFN-β and endogenous IFN-β, potentially impairing antiviral immunity.

Objectives: To investigate whether NAbs against IFN-β occur in multiple sclerosis patients that developed natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML).

Methods: Seven NTZ-PML patients were matched with natalizumab-treated patients with prior IFN-β exposure. All were tested for NAbs against IFN-β in serum.

Results: NAbs against IFN-β were absent in all NTZ-PML cases, but present in three matched patients.

Conclusions: These findings do not suggest a contributing role for IFN-β NAbs in natalizumab-associated PML.

Keywords: Immunogenicity; Interferon-beta; Multiple sclerosis; Natalizumab; Progressive multifocal leukoencephalopathy.

MeSH terms

  • Adult
  • Antibodies* / blood
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Female
  • Humans
  • Immunologic Factors* / adverse effects
  • Immunologic Factors* / immunology
  • Immunologic Factors* / therapeutic use
  • Interferon-beta* / immunology
  • Interferon-beta* / therapeutic use
  • Leukoencephalopathy, Progressive Multifocal* / blood
  • Leukoencephalopathy, Progressive Multifocal* / chemically induced
  • Leukoencephalopathy, Progressive Multifocal* / immunology
  • Male
  • Middle Aged
  • Multiple Sclerosis* / blood
  • Multiple Sclerosis* / complications
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis* / immunology
  • Natalizumab / therapeutic use

Substances

  • Natalizumab
  • Interferon-beta
  • Immunologic Factors
  • Antibodies, Monoclonal, Humanized
  • Antibodies