GFAPα IgG-associated encephalitis upon daclizumab treatment of MS

Area of Science:

• Neuroimmunology
• Neurology
• Autoimmune Diseases

Background:

• Daclizumab, a CD25-targeting therapy for multiple sclerosis (MS), has been associated with serious central nervous system (CNS) inflammatory disorders.
• Glial fibrillary acidic protein alpha (GFAPα) immunoglobulin G (IgG)-associated encephalitis is a rare but severe autoimmune condition affecting the brain.

Purpose of the Study:

• To describe a case of GFAPα IgG-associated encephalitis in a patient treated with daclizumab for MS.
• To summarize characteristics of additional German MS cases with severe encephalitis and a US case of CNS vasculitis linked to daclizumab.

Main Methods:

• Case evaluation focusing on etiology, clinical presentation, and treatment response.
• Cerebrospinal fluid (CSF) analysis for inflammatory markers and GFAPα IgG antibodies.
• Review of additional patient data and published literature.

Main Results:

• Six patients (4 female, 2 male; median age 38) presented with progressive neuropsychologic/neurologic deficits.
• CSF revealed pleocytosis, elevated protein, and GFAPα IgG antibodies (not in serum).
• Three patients had rash with eosinophilia; two showed active demyelination. The described case was steroid-responsive.

Conclusions:

• Daclizumab-associated encephalitis, including GFAPα IgG astrocytopathy, represents severe secondary CNS autoimmunity.
• Interference with NK cells and Tregs by anti-CD25 therapy may precipitate such autoimmune events.
• Prompt diagnosis and management are crucial for potential recovery.