Abstract Details

Title Identification of SKOR2 IgG as a Novel Biomarker of Paraneoplastic Neurologic Syndrome

Topic Autoimmune Neurology

Presentation(s) N1 - Neuroscience in the Clinic: Emerging Autoantibodies in Neurologic Disease (3:45 PM-3:55 PM)

Poster/Presentation
Number 001

Background PNS are group of disorders affecting any level of the neuroaxis associated with underlying tumors. Recently, wide variety of neurological presentations and autoantibodies have been associated with PNS. Development of novel autoantigen discovery techniques, like programmable phage immunoprecipitation sequencing (PhIP-Seq) has led to identification of novel putative autoantigens such as kelch-like protein 11 (KLHL11). Herein, we report the discovery of novel autoantibodies targeting SKOR2 protein in two patients diagnosed with CNS autoimmunity and underlying malignancy utilizing PhIP-Seq.

Objective

To report identification of a novel biomarker of paraneoplastic neurologic syndrome (PNS), Sloan-Kettering-Virus-Family-Transcriptional-Corepressor-2 (SKOR2)-IgG.

Design/Methods Stored specimens with unclassified staining at the junction of Purkinje cell and granule cell layers were analyzed by PhIP-Seq for putative autoantigen identification. The autoantigen was confirmed utilizing recombinant antigen expressing cell-based assay (CBA), western blotting, and tissue immunofluorescence assay (IFA) colocalization. Additionally, we performed thorough clinical validation utilizing healthy and disease/cancer control samples.

Results

PhIP-Seq data revealed SKOR2 as the candidate autoantigen. The target antigen was confirmed using recombinant SKOR2-expressing CBA, and cell lysate western blot. Furthermore, IgG from both patients’ samples colocalized with commercial SKOR2–specific IgG on mouse brain cryo-sections. Both the SKOR2-IgG positive patients had CNS involvement; one presenting with encephalitis and seizures (patient 1) and the other with cognitive dysfunction, spastic ataxia, dysarthria, dysphagia, and pseudobulbar affect (patient 2). They had a refractory progressive course and were diagnosed with adenocarcinoma (patient 1: lung, patient 2: gall bladder). Histopathological assessment of the lung adenocarcinoma tissue (case 1) revealed cytoplasmic and nuclear SKOR2 immunoreactivity in the tumor cells. Sera from adenocarcinoma patients without PNS (n=30) tested for SKOR2-IgG were negative.

Conclusions

SKOR2-IgG represents a novel biomarker for PNS associated with adenocarcinoma. Identification of additional SKOR2-IgG positive cases will aid in categorization of associated neurological phenotype and risk of underlying malignancy.

Authors/Disclosures
Mohamed M. Rezk, MD (utmb) PRESENTER	Dr. Rezk has nothing to disclose.
Sean J. Pittock, MD (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. 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 Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. 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 $500-$4,999 for serving as a Consultant for Roche/Genentech. 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, Inc. 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 Hoffman/LaRoche AG. 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 Genetech. 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 F. Hofman/LaRoche. 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 research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. 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.
Ronak K. Kapadia, MD	Dr. Kapadia has nothing to disclose.
Andrew Knight	No disclosure on file
Yong Guo	No disclosure on file
Pranjal Gupta, MD	Dr. Gupta has nothing to disclose.
Reghann LaFrance-Corey	No disclosure on file
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic)	The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou 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.
Surendra Dasari	No disclosure on file
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.
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.