Abstract Details

Title Uncovering the putative pathogenesis of Stiff Person Syndrome (SPS): is there a neuroinflammatory mechanism?

Topic Autoimmune Neurology

Presentation(s) P13 - Poster Session 13 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-007

Background

SPS is frequently a disabling neurological disorder that is associated with anti-GAD65 autoimmunity. Immune derangement involving both B and T cells have been hypothesized in the pathogenesis of SPS. Notably, immunotherapy response is heterogenous and it is unclear whether there is a primary inflammatory component present that is helping drive the disease.

Objective

To determine the profile of immune mediators (e.g., cytokines, chemokines) in the CSF of people with Stiff Person Syndrome (SPS).

Design/Methods

The profile of 36 cytokines and chemokines was assessed in the CSF of 20 GAD65 seropositive SPS patients, 10 MS and 10 non-inflammatory control subjects. Non-parametric statistical analysis (Kruskal-Wallis test) and principal component analysis (PCA) were used to identify significant increases of immune mediators in the SPS group compared to controls and study inter-sample and inter-protein correlations.

Results

Most of the SPS cases exhibited the classic phenotype (90%, n= 18) and were treatment naïve (80%, n= 16). Anti-GAD-65 antibody was positive in the CSF of 11 (55%) SPS subjects, while oligoclonal bands in CSF were present in 5 SPS cases (25%). PCA showed a heterogeneous spread with the SPS samples overlapping MS and non-inflammatory controls. There were no significant increases of cytokines or chemokines among the SPS cases.

Conclusions

Although there are hints of intrathecal inflammation in a subset of SPS patients, this preliminary analysis of cytokines and chemokines does not support the presence of a cytokine-mediated pathway of inflammation within the CSF compartment. Studies are needed to evaluate whether a strong inflammatory component exists within the periphery of individuals with SPS.

Authors/Disclosures
Maria I. Reyes, MD (Hospital Simon Bolivar) PRESENTER	Dr. Reyes has nothing to disclose.
Samantha Hao, MD	Ms. Hao has nothing to disclose.
Susana Dominguez Penuela, MD (Johns Hopkins University School of Medicine)	Dr. Dominguez Penuela has nothing to disclose.
David Acero-Garces, MD (Johns Hopkins University)	The institution of Dr. Acero-Garces has received research support from Ministry of Science, Technology and Innovation of Colombia.
Carlos A. Pardo-Villamizar, MD (Johns Hopkins U, Med Dept of Neurology)	The institution of Dr. Pardo-Villamizar has received research support from National Institutes of Health. The institution of Dr. Pardo-Villamizar has received research support from Bart McLean Fund for Neuroimmunology Research .
Scott D. Newsome, DO, FAAN (Johns Hopkins Hospital)	Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Newsome has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. The institution of Dr. Newsome has received research support from Biogen. The institution of Dr. Newsome has received research support from Genentech/Roche. The institution of Dr. Newsome has received research support from Department of Defense. The institution of Dr. Newsome has received research support from Patient Centered Outcomes Research Institute. The institution of Dr. Newsome has received research support from National MS Society. The institution of Dr. Newsome has received research support from The Stiff Person Syndrome Research Foundation. The institution of Dr. Newsome has received research support from Lundbeck. Dr. Newsome has received personal compensation in the range of $10,000-$49,999 for serving as a Lead PI for Clinical Trial with Roche.