Autoimmune Neurological Diseases and Those Secondary to Immunotherapy: Study of Immunological Mechanisms and Research Into Targets of Immune Attack

Maladies Neurologiques Auto-immunes et Secondaires à l'immunothérapie : étude Des mécanismes Immunologiques et Recherche Des Cibles de l'Attaque Immune

The pathophysiology of neurological toxicities secondary to immune checkpoint inhibitors (ICIs) is unknown. Various mechanisms have been proposed: activation of cytotoxic CD8 T cells, autoantibodies via activation of B cells and CD4 cells, non-specific inflammation through the production of pro-inflammatory cytokines, and complement activation.

The aim of this research is to characterise the pathophysiological mechanisms of neurotoxicities in cancer patients treated with ICIs.

Inclusion Criteria:

• Adult patient (aged ≥ 18 years)
• Affiliated with a social security scheme
• Express consent to participate in the study
• Indication for lumbar puncture And
• Patients with cancer, undergoing treatment with ICIs, presenting neurological symptoms after starting treatment with ICIs. These symptoms must have appeared no more than 3 months after the last administration of ICIs.

Or

• Patients with an autoimmune disease of the central nervous system (diagnosis made by teams 1, 2 and 3) according to internationally recognised criteria, with no history of active cancer in the last 3 years and no other autoimmune disease Or
• Patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hypertension (diagnosed based on imaging (brain MRI) and clinical findings), with no history of active cancer in the last 3 years and no active autoimmune disease

Exclusion Criteria:

• Contraindication or refusal to perform a lumbar puncture
• Sample not suitable for research (volume of CSF collected for treatment >5 mL)
• Corticosteroid therapy or other immunomodulatory treatment in progress (discontinued less than 15 days prior to inclusion)
• Pregnant or breastfeeding women
• Not affiliated with the social security system, patients under French State Medical Aid for undocumented migrants
• Patients under guardianship or curatorship, under judicial protection measures, or deprived of their liberty by judicial or administrative decision