Neuroglial Biomarkers in GAD65-IgG-Associated Stiff-Person Syndrome and Cerebellar Ataxia
Yahel Segal1, Binxia Yang2, Vanessa Pazdernik3, Divyanshu Dubey1, Eoin Flanagan1, John Mills1, Andrew McKeon1, Sean Pittock1, Anastasia Zekeridou1
1Department of Laboratory Medicine and Pathology, Department of Neurology, Center for MS and Autoimmune Neurology, 2Department of Laboratory Medicine and Pathology, 3Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic
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.
Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.