Paraneoplastic Calmodulin Kinase-Like Vesicle-Associated Protein (CAMKV) Autoimmune Encephalitis

Area of Science:

• Neuroimmunology
• Onconeurology
• Autoantibody-mediated neurological disorders

Background:

• Autoimmune encephalitis presents a diagnostic challenge, often requiring identification of specific autoantibodies.
• Paraneoplastic syndromes can manifest with diverse neurological symptoms, complicating diagnosis and treatment.

Purpose of the Study:

• To characterize a novel autoimmune paraneoplastic encephalitis associated with antibodies targeting the calmodulin kinase-like vesicle-associated (CAMKV) protein.
• To investigate the clinical features, oncologic associations, and treatment response in patients with CAMKV-IgG.

Main Methods:

• Serum and CSF samples were screened using indirect immunofluorescence assay and human protein microarrays.
• Candidate antigen CAMKV was validated through Western blot, confocal microscopy, immune-absorption, and mass spectrometry.
• Recombinant CAMKV-specific assays confirmed antibody specificity.

Main Results:

• Five patients with CAMKV-IgG positive encephalitis were identified, presenting with altered mental status, seizures, and movement disorders.
• Neuroimaging revealed characteristic MRI abnormalities, including mesial temporal lobe hyperintensities.
• Associated cancers included uterine adenocarcinoma (3), bladder urothelial carcinoma (1), and non-Hodgkin lymphoma (1).

Conclusions:

• Calmodulin kinase-like vesicle-associated (CAMKV) immunoglobulin G (IgG) is a biomarker for a distinct form of paraneoplastic encephalitis.
• This encephalitis exhibits immunotherapy responsiveness and is frequently associated with uterine malignancies.
• The findings highlight CAMKV-IgG as a crucial diagnostic and therapeutic target in onconeurology.