Abstract Details

Title Autoantibody Profiling of Paraneoplastic Neurological Syndrome Sera Reveals ERVK7-IgG as a Germ Cell Tumor Associated Biomarker

Topic Autoimmune Neurology

Presentation(s) S16 - Autoimmune Neurology: Immune Profiling and Antibody Detection (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Objective To identify novel autoantibody biomarkers in patients with paraneoplastic neurologic syndromes (PNS) associated with germ cell tumors (GCTs), and to evaluate their prevalence as GCT-specific serological markers in a broader tumor cohort.

Background Ma2-IgG, KLHL11-IgG, LUZP4-IgG and NMDA-R-IgG are known as GCT-related PNS autoantibodies. Leveraging tumor-specific immune response in PNS may enable discovery of GCT-specific biomarkers that improve tumor detection and disease monitoring.

Design/Methods

Serum samples from patients with confirmed GCT-related PNS were screened using phage immunoprecipitation sequencing (PhIP-Seq) to identify cancer-specific IgGs. Candidate antigen was validated by enzyme-linked immunosorbent assay (ELISA), followed by testing in a larger GCT and other cancer cohort without PNS to assess tumor specificity.

Results

Thirteen male patients (median age 48 years; range 29–84) with GCTs and KLHL11-IgG (n=12) and/or LUZP4-IgG (n=4) PNS were screened by PhIP-Seq, revealing antibody binding to distinct regions of the endogenous retrovirus group-K member-7 envelope protein (ERVK-7). In an independent set of 24 GCT-related PNS cases, 10 were ERVK-7-IgG–positive by ELISA, including 6 that were PhIP-Seq–positive. Among 358 GCT patients without PNS, 56 (16%) were ERVK-7-IgG positive, spanning multiple histologic subtypes most frequently seminoma (41%), followed by mixed GCT (21%) and embryonal carcinoma (18%). One ERVK-7-IgG positive woman had an ovarian teratoma. Specificity testing across autoimmune, oncologic, and healthy control sera showed minimal false positive rate (3/281, 1%). ERVK-7 expression was confirmed by IHC in GCT tissue, supporting tumor origin of the immune response.

Conclusions ERVK-7-IgG represents a novel GCT-associated autoantibody emerging from PNS cases and extending to broader GCT subsets, especially seminomas. Its detection may aid early diagnosis of GCTs, particularly in patients with neurologic symptoms or negative standard tumor markers. Notably, ERVK-7-IgG targets an endogenous retroviral envelope protein, suggesting an immune response against tumor-expressed endogenous retroviral antigens.

Authors/Disclosures
Haidara Kherbek, MD PRESENTER	Haidara Kherbek 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.
Andrew Knight	Andrew Knight has nothing to disclose.
Brian Costello (Mayo Clinic)	Brian Costello has nothing to disclose.
Silvana B. De Lorenzo, PhD	Dr. De Lorenzo has nothing to disclose.
Bradley Leibovich, MD	Dr. Leibovich has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Telix.
John Cheville	John Cheville has nothing to disclose.
Yong Guo	Yong Guo has nothing to disclose.
Jessica A. Sagen, MA (Mayo Clinic)	Ms. Sagen has nothing to disclose.
Rory Olson, PhD	Dr. Olson has nothing to disclose.
Alicia Algeciras-Schimnich	Alicia Algeciras-Schimnich has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Diagnostics. Alicia Algeciras-Schimnich has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fujirebio Diagnostics. Alicia Algeciras-Schimnich has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Diagnostics.
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.
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.
Surendra Dasari	Surendra Dasari has nothing to disclose.
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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