Abstract Details

Title TRIM46 autoantibody: expanded neurological phenotype and oncological associations

Topic Autoimmune Neurology

Presentation(s) Autoimmune Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 020

Objective To report neurological presentations and oncological associations of tripartite motif 46 (TRIM46)-IgG seropositive patients.

Background

Three patients with autoimmune neurological syndromes accompanied by TRIM46 (neuronal axonal initial segment [AIS] protein)-reactive IgG have been described. Two had small cell lung cancer [SCLC]).

Design/Methods

Candidate archived encephalopathic patient sera had yielded, in clinical lab testing on cryosectioned mouse tissues (Tissue-based IFA), a neural-specific immunofluorescence staining pattern consistent with AIS. Further evaluation by phage immunoprecipitation sequencing (PhiP-Seq) identified TRIM46 as the autoantigen; specificity was confirmed using recombinant proteins.

Results 15 patients (10 female; clinical information available for 14) were confirmed to have TRIM46-IgG by TIFA and transfected COS7 cell-based IFA (serum, n=8; CSF, n=6; both, n=1). Median age, 68 years (range 25-87). All were suspected to have a paraneoplastic neurological syndrome. Eleven (79%) presented with a subacute cerebellar syndrome (4 isolated; 3 with additional encephalopathic signs, 1 brainstem signs, 1 parkinsonism, 1 lower extremity hyperreflexia and bladder dysfunction, 1 paraparesis. Three individual patients presented with limbic encephalitis, seizures or tetraparesis. Brain MRI was abnormal in 5/8 imaged patients: 4 had cerebellar atrophy and 1 had bilateral medial temporal T2/FLAIR hyperintensities. CSF was inflammatory (elevated leucocyte count and/or CSF-restricted supernumerary oligoclonal bands) in 5/6 patients. Ten patients (71%) had a malignancy (4 diagnosed before neurological onset and 6 newly discovered). Tumors included pancreatic neuroendocrine carcinoma (n=3), SCLC (n=2), sarcoma (n=2), lung adenocarcinoma (n=1), gastrointestinal tumor (n=1), ovarian carcinoma (n=1). One additional patient had multiple pulmonary nodules, and one had hilar lymphadenopathy (no histopathological diagnosis established).

Conclusions

This study confirms that TRIM46-IgG is a specific biomarker of paraneoplastic neurological syndrome. Its oncological association is not limited to SCLC. The most common neurological presentation was cerebellar ataxia, often with additional CNS signs, and occasionally a different CNS presentation.

Authors/Disclosures
Cristina Valencia Sanchez, MD (Mayo Clinic Arizona) PRESENTER	Dr. Valencia Sanchez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG therapeutics. Dr. Valencia Sanchez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Valencia Sanchez has a non-compensated relationship as a member of the medical advisory board with The MOG Project that is relevant to AAN interests or activities.
Andrew Knight	Andrew Knight has nothing to disclose.
M Bakri Hammami, MD (Moffitt Cancer Center)	Dr. Hammami has received intellectual property interests from a discovery or technology relating to health care.
John R. Mills, MD, PhD (Mayo Clinic)	The institution of Dr. Mills has received research support from Werfen Diagnostics. Dr. Mills has received intellectual property interests from a discovery or technology relating to health care.
Vanda Lennon, MD, PhD (Mayo Clinic)	The institution of Dr. Lennon has received research support from NIH. Dr. Lennon has received intellectual property interests from a discovery or technology 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.
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 Arialys. 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. 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. 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.
Divyanshu Dubey, MD, FAAN (Mayo Clinic)	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.

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