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Abstract Details

Presymptomatic Aquaporin-4 (AQP4) Autoantibody Seropositivity in NMOSD: Analysis of the Department of Defense Serum Repository (DoDSR)
S50 - Autoimmune Neurology: NMOSD
NMOSD is an autoimmune disease primarily targeting the spinal cord and optic nerve, leading to paralysis and blindness. Antibodies directed against AQP4 are a key element of disease pathogenesis and provide a disease-specific marker of NMOSD pathology. One small study of patients with myasthenia gravis suggested that antibodies to AQP4 may be present as long as 16 years prior to onset of NMOSD; however, difficulty obtaining pre-symptomatic serum samples for rare diseases has limited our ability to test for the presymptomatic presence of this biomarker.
Determine whether antibodies to AQP4 are present in pre-symptomatic serum from patients with neuromyelitis spectrum disorder (NMOSD) in the DoDSR
Subjects were identified through the DoD/Defense Medical Surveillance System (DMSS) utilizing ICD codes for Neuromyelitis Optica (ICD-9: 341.0, ICD10: G36.0). After verifying the clinical and laboratory records of each patient to ensure the correct diagnosis, a list of these potential subjects was sent to the Armed Forces Health Surveillance Division (AFHSD) to determine which had serum specimens. Serum from these patients, as well as age and sex-matched healthy and disease (multiple sclerosis) controls, was acquired from the DoDSR at the time closest to diagnosis and at timepoints up to 20 years prior to diagnosis.  Serum from these samples was analyzed for AQP4 antibodies using Euroimmun fixed cell-based assays performed at ARUP. 
64 people who met inclusion criteria were identified and analyzed for autoantibodies to AQP4. Of 32 AQP4-positive patients analyzed for seropositivity in the sample prior to disease onset, 20 (62.5%) were positive for AQP4 (mean -940 days, SD -400.5); analysis of older serum samples will be presented at the conference. 
Antibodies to AQP4 are present in a subset of patients with NMOSD years prior to diagnosis. Additional studies are needed to determine what factors predict onset of disease.
Authors/Disclosures
Tammy L. Smith, MD, PhD (Imaging and Neurosciences Center)
PRESENTER 		The institution of Dr. Smith has received research support from Alexion/AstraZeneca.
John W. Rose, MD, FAAN (Imaging and Neurosciences Center) The institution of Dr. Rose has received research support from National Multiple Sclerosis Society. The institution of Dr. Rose has received research support from Guthy Jackson Charitable Foundation. The institution of Dr. Rose has received research support from NIH . The institution of Dr. Rose has received research support from VA. The institution of Dr. Rose has received research support from Biogen. The institution of Dr. Rose has received research support from Friends of MS. Dr. Rose has received intellectual property interests from a discovery or technology relating to health care.
Sean J. Pittock, MD (Mayo Clinic Dept of Neuro) Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. 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, Inc. 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 Hoffman/LaRoche AG. 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 Genetech. 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 F. Hofman/LaRoche. 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 research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. 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.
Nathan Tagg, MD (Duke Eye Center) Dr. Tagg has stock in Apple, Birkshire Hathaway, Medtronic.
Stacey Clardy, MD, PhD, FAAN (University of Utah) Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca/Alexion. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen/Horizon. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from NIH/NINDS. The institution of Dr. Clardy has received research support from SRNA. The institution of Dr. Clardy has received research support from Alexion/AstraZeneca. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with Barrow Neurological Institute. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with Beaumont Health. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with Stanford. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with Cleveland Clinic.
Noel Carlson, PhD (VA SLC HCS) The institution of Mr. Carlson has received research support from Biogen. Mr. Carlson has received personal compensation in the range of $100,000-$499,999 for serving as a Employee as a Researcher with Veteran Affairs.
Ka-Ho Wong (U of U Neurology Clinic) Mr. Wong has nothing to disclose.
Keith Groshans, MD (Madigan Army Medical Center) Dr. Groshans has nothing to disclose.
David Edward Horvat, MD (Walter Reed National Military Medical Center) Dr. Horvat has nothing to disclose.
Lisa Kay Peterson, PhD (ARUP Laboratories) The institution of Dr. Peterson has received research support from Kronus.
Sithembile Mabila, PhD (Defense Health Agency, Armed Forces Health Surveillance Division) Dr. Mabila has nothing to disclose.