Abstract Details

Title A Prospective Clinical Validation of Neuronal Intermediate Filament IgGs

Topic Autoimmune Neurology

Presentation(s) S16 - Autoimmune Neurological Disorders: Diagnosis, Biomarkers, and Epidemiology (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Objective

To prospectively validate neuronal intermediate filament (NIF)-IgGs (alpha internexin [α-IN], neurofilament light [NF-L] chain, and heavy [NF-H] chain) as paraneoplastic neurological biomarkers (December 2017 – May 2019).

Background Our previous study demonstrated high specificity by a 2-step diagnostic algorithm (100% for CSF): 1) pattern-specific IgG staining of murine tissue (indirect immunofluorescence assay [IFA]); 2) NIF-specific cell-based assay (CBA) confirmation. The clinical value of serum, CSF and different NIF-IgG profiles remained uncertain.

Design/Methods

We prospectively identified 38 NIF-IgG positive patients (41 of 131988 specimens positive [0.03%]: 17/26 serums [65%]; 24/26 CSF [92%]).

Results Among 38 NIF-IgG positive patients, 21 were men (55%); median age of disease onset was 60 years (range, 19-88). For CNS autoimmune diagnoses (29: encephalopathy, 19; cerebellar ataxia, 9; and myelopathy, 1) CSF was more sensitive (95%, 21/22) than serum (61%, 11/18), p = 0.0002. Five patients had autoimmune neuropathies: axonal sensorimotor (3), trigeminal (1), and autonomic gastrointestinal (1). All 3 patients with CSF available were NIF-IgG positive (including 1 that was serum negative). Of 4 with non-autoimmune disorders (metabolic encephalopathy, 2; ALS, 1; diffuse Lewy body disease, 1) a solitary CSF available was negative. Seven of 9 patients with rhombencephalopathy (78%) were NF-L-IgG positive, as compared to 8/29 with other phenotypes (24%), p = 0.02. Neuroendocrine-lineage carcinomas predominated (8/10 cases, 75%): small cell, 4; Merkel cell, 2; neuroendocrine, 2 (pancreas and small bowel, 1 each). The remaining 2 neoplasms were: hepatocellular carcinoma, 1; lymphoma, 1. Eight of 10 NF-L-IgG positive patients had cancer detected (80%), and 7/23 NF-L-IgG negative patients did not (30%), P = 0.002.

Conclusions CNS disorders predominate in NIF autoimmunity. CSF testing is more sensitive than serum for paraneoplastic neurologic autoimmunity (as well as more specific, as previously shown). NF-L-IgG is predictive of ataxic disorders in the setting of neuroendocrine-lineage neoplasia.

Authors/Disclosures
Eati Basal PRESENTER	Eati Basal has nothing to disclose.
	No disclosure on file
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Andrew McKeon, MD (Mayo Clinic)	The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.

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