Abstract Details

Title Blood-Brain Barrier Dysfunction and CSF Immunoglobulin Synthesis in Down Syndrome Regression Disorder

Topic General Neurology

Presentation(s) P7 - Poster Session 7 (5:00 PM-6:00 PM)

Poster/Presentation
Number 2-010

Objective

This study sought to evaluate proteomic, metabolomic, and immune signatures in the cerebrospinal fluid of individuals with Down Syndrome Regression Disorder (DSRD).

Background Down Syndrome Regression Disorder (DSRD) is an acute/subacute onset neuropsychiatric condition affecting individuals with Down syndrome. This condition has been previously noted to have abnormalities on multiple neurodiagnostic tests including EEG, MRI and lumbar puncture which are associated with marked responses to immunotherapy when present.

Design/Methods A prospective case-control study comparing proteomic, metabolomic, and immune profiles in individuals with DSRD was performed. Samples were obtained from a biorepository of affected individuals and compared to clinically available data and previously obtained neurodiagnostic studies. Individuals with DSRD were compared to individuals with established neuroinflammatory conditions (e.g., multiple sclerosis), and neurotypical controls undergoing a lumbar puncture for headaches. Samples underwent high-throughput proteomic, metabolomic, and immune marker profiling. Data was compared across groups and clinical phenotypes. Gene set enrichment analysis and pathway analyses were utilized to analyze the data.

Results In total, 34 individuals with DSRD, 22 neuroinflammatory controls, and 27 neurotypical controls were enrolled in the study. We observed a highly significant concordance in dysregulated proteomics signatures in DSRD and neuroinflammatory controls versus healthy controls, most prominently upregulation of many immunoglobulin sequences. In addition, individuals with DSRD displayed strong upregulation of liver-derived plasma proteins and erythrocyte proteins in the CSF, indicating poor blood-brain barrier integrity. The immune marker profile of DSRD is clearly similar to other neuroimmunological conditions, including strong elevation of MIP3-a, eotaxin, and IFN-g.

Conclusions Individuals with DSRD have unique CSF proteomic and metabolomic signatures consistent with neuroinflammation and increased blood-brain barrier permeability. The CSF of individuals with DSRD was more comparable to individuals with neuroinflammatory disorders than neurotypical controls, indicating the potential for an immune etiology of disease.

Authors/Disclosures
Shermila Pia, MD PRESENTER	Dr. Pia has nothing to disclose.
Jonathan Santoro, MD (Department of Neurology, Children's Hospital Los Angeles)	Dr. Santoro has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Santoro has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cycle Pharma. Dr. Santoro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Santoro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for National Down Syndrome Society.
Neetha Paul Eduthan, MS	Ms. Paul Eduthan has nothing to disclose.
Mellad Khoshnood, MD (Children's Hospital Los Angeles)	Dr. Khoshnood has nothing to disclose.
Saba Jafarpour, MD (Children’s Hospital of Los Angeles)	Dr. Jafarpour has nothing to disclose.
Natalie Boyd (Children's Hospital Los Angeles)	Natalie Boyd has nothing to disclose.
Benjamin Vogel	Benjamin Vogel has nothing to disclose.
Lina Nguyen (Children's Hospital Los Angeles)	Lina Nguyen has nothing to disclose.
Lilia Kazerooni, BS	Miss Kazerooni has nothing to disclose.
Eleanor Britton	Miss Britton has nothing to disclose.
Hannah Lyford	Miss Lyford has nothing to disclose.
Matthew Galbraith, PhD	The institution of Dr. Galbraith has received research support from NIH.
Angela Rachubinski, PhD	The institution of Dr. Rachubinski has received research support from NIH.
Joaquin Espinosa	Joaquin Espinosa has received personal compensation in the range of $0-$499 for serving as a Consultant for Biohaven.

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