Abstract Details

Title Complement Dysregulation in Stiff Person Syndrome: Pathophysiological Insights

Topic Autoimmune Neurology

Presentation(s) S16 - Autoimmune Neurology: Immune Profiling and Antibody Detection (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Objective To investigate complement activation in the cerebrospinal fluid (CSF) and plasma of Stiff Person Syndrome (SPS) patients to inform on the immune profile.

Background SPS is a rare autoimmune neurologic disorder characterized by progressive muscle stiffness and painful muscle spasms. The underlying pathophysiology is elusive, and while autoantibodies are commonly implicated, the role of complement activation in SPS remains poorly understood.

Design/Methods

We analyzed complement components in the plasma of patients with SPS (n=32), healthy controls (n=14), and patients with other central nervous system (CNS) disorders including multiple sclerosis (n=15). We also compared paired CSF and plasma samples in SPS (n = 5) and controls (n = 8). Quantified markers included C3, C3b, C4b, Factor D, C5, Factor H, and Properdin. Statistical comparisons were performed using ANOVA and ROC curve analysis.

Results SPS patients exhibited distinct complement activation patterns between CSF and plasma. In CSF, levels of C3, C3b/iC3b, C4b, and Factor D were elevated, while C5, Factor H, and Properdin were significantly lower compared to plasma. Plasma levels of C3 and C4 were markedly decreased in SPS versus healthy controls (p< 0.0001). When comparing SPS to both healthy and other neurological disorder (OND) groups, Factor B, Factor H, and Factor I levels were significantly reduced (p< 0.0001). ROC analysis identified Factor I as a robust biomarker for SPS, with an AUC of 0.863, indicating strong discriminatory power. A combined panel of C4, C5, and C9 demonstrated a strong biomarker potential for SPS (AUC = 0.88 vs. healthy; AUC = 0.9583 vs. OND).

Conclusions Our findings reveal abnormal complement activation in SPS, with differential expression across CSF and plasma compartments. C4, C5, C9, and Factor I emerge as promising biomarkers for distinguishing SPS from healthy and other neurological controls, offering potential for improved diagnostic precision and therapeutic targets.

Authors/Disclosures
Amanda L. Piquet, MD, FAAN (University of Colorado) PRESENTER	The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kyverna . The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech/Roche. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna. The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Sands Anderson PC. Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Joe Jones Law Firm. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cortez & Associates. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Falk Waas. The institution of Dr. Piquet has received research support from Rocky Mountain MS Center. The institution of Dr. Piquet has received research support from Roche/Genentech. The institution of Dr. Piquet has received research support from NYU. The institution of Dr. Piquet has received research support from Anokion. The institution of Dr. Piquet has received research support from UCB . The institution of Dr. Piquet has received research support from Foundation for Sarcoidosis. The institution of Dr. Piquet has received research support from Kyverna . Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Litigative Consultant with US-Dept HHS/DICP. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Autoimmune Encephalitis Alliance (AEA) that is relevant to AAN interests or activities. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Stiff Person Syndrome Research Foundation (SPSRF) that is relevant to AAN interests or activities.
Brendan Freitas, PhD	An immediate family member of Dr. Freitas has received personal compensation for serving as an employee of Pfizer. An immediate family member of Dr. Freitas has received personal compensation for serving as an employee of Think Bioscience. An immediate family member of Dr. Freitas has stock in Pfizer. Dr. Freitas has received intellectual property interests from a discovery or technology relating to health care.
Jackson Tumas French	Mr. Tumas French has nothing to disclose.
Sean Selva	Sean Selva has nothing to disclose.
Jadyn Zook, PRA	Ms. Zook has nothing to disclose.
Sadie Eggmann	Sadie Eggmann has nothing to disclose.
Xiaoli Yu, PhD (University of Colorado Anschutz Medical Campus)	The institution of Dr. Yu has received research support from NIH.

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