Abstract Details

Title Neuroglial Biomarkers in GAD65-IgG-Associated Stiff-Person Syndrome and Cerebellar Ataxia

Topic Autoimmune Neurology

Presentation(s) P3 - Poster Session 3 (11:30 AM-12:30 PM)

Poster/Presentation
Number 1-007

Objective

To characterize serum neuroglial biomarker profiles in GAD65-IgG-associated stiff-person syndrome (SPS) and cerebellar ataxia, compare levels across clinical phenotypes, and explore clinical associations.

Background

GAD65-IgG-associated SPS and cerebellar ataxia are clinically distinct disorders that share a common antibody but differ in disease course and response to immunotherapy. There are currently no validated biomarkers of disease activity to guide treatment decisions.

Design/Methods

Serum sTREM2, YKL-40, UCHL1, GFAP, and NfL were measured using an automated immunoassay (Ella, Biotechne) in a cross-sectional cohort of clinically characterized patients with GAD65-IgG-associated SPS, cerebellar ataxia, or mixed SPS-ataxia phenotype. Age-stratified reference values were established from 75 healthy controls. Biomarker levels were compared between patients and controls and across phenotypes. Associations with clinical characteristics were investigated. Longitudinal analyses are ongoing.

Results

Serum samples from 132 patients were analyzed, including 70 with SPS, 48 with cerebellar ataxia, and 14 with mixed SPS-ataxia phenotype. Compared with controls, GAD65-IgG patients showed significant elevations in sTREM2 (median 22,813 pg/mL vs 15,669 pg/mL, P<0.01), YKL-40 (median 42,623 pg/mL vs 29,963 pg/mL, P<0.01), UCHL1 (median 108.5 pg/mL vs 61.6 pg/mL, P<0.01), GFAP (median 8.88 pg/mL vs 1.66 pg/mL, P<0.01) and NfL (median 30.7 pg/mL vs 15.85 pg/mL, P<0.01) . Biomarker levels did not correlate with modified Rankin Scale score or gait-aid requirement, and differences across phenotypes were not statistically significant. Within GAD65-IgG patients, biomarker levels were positively correlated, strongest for GFAP with NfL (r=0.65), sTREM2 with NfL (r=0.55), and sTREM2 with GFAP (r=0.48).

Conclusions GAD65-IgG-associated SPS and cerebellar ataxia demonstrate elevated serum markers of astroglial and neuroaxonal injury. While these biomarkers did not correlate with global disability measures in this cross-sectional cohort, inter-marker correlations suggest coordinated neuroglial pathology. Longitudinal analyses are underway to investigate whether these biomarkers are associated with disease activity over time.

Authors/Disclosures
Yahel Segal, MD (Mayo Clinic) PRESENTER	Dr. Segal has nothing to disclose.
Binxia Yang (Mayo clinic)	Binxia Yang has nothing to disclose.
Vanessa Pazdernik, MS	Ms. Pazdernik 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.
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic)	The institution of Dr. Flanagan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Merck. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received intellectual property interests from a discovery or technology relating to health care. Dr. Flanagan has received intellectual property interests from a discovery or technology relating to health care. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology that is relevant to AAN interests or activities.
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.
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.
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.

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