To report a novel autoimmune encephalitis associated with neuronal antibodies targeting Fibrinogen C domain-containing protein 1 (FIBCD1).

Autoimmune encephalitides represent a growing group of immune-mediated neurological disorders. Despite the identification of novel antibodies, a subset of patients remains antibody-negative after extensive testing.

We identified a new antibody target, FIBCD1 (a transmembrane protein involved in innate immunity and neuronal function), in all six patients. All patients (median age 55.5 years, range 50-76; four female) had seizures and cognitive symptoms, associated in 4/6 with psycho-behavioral and/or mood disturbances. None had an underlying tumor. Brain MRI was abnormal in 4/6 patients (two with inflammatory lesions in temporal lobes, two with atrophy) and CSF was unremarkable except for CSF-restricted oligoclonal bands in 2/6. Four patients received immunotherapy (one first-line only, and three both first- and second-line), showing a partial response. At last follow-up (median 32 months, range 24-96), 4/6 patients had persistent seizures and/or cognitive impairment. FIBCD1 antibodies were found by CBA in all paired serum/CSF of patients, but in none of the 282 controls (60 healthy subjects, 222 with other neurological diseases).