Abstract Details

Title What Is the Frequency of "Truly" AQP4-IgG-Negative NMO and Does It Differ Phenotypically from Seropositive Disease?

Topic MS and Related Diseases

Presentation(s) P02 - (-)

Poster/Presentation
Number 136

Objective

Background BACKGROUND: AQP4-IgG is a clinically validated biomarker unifying NMO spectrum disorders. Assay sensitivities/specificities vary. False negativity invalidates phenotype comparisons.

Design/Methods DESIGN/METHODS: From 2005-2011, 5349 samples from Mayo Clinic patients were tested by IIF assay. Clinical records identified 159 patients with NMO. Of those, 109 (69%) were positive and 50 (31%) negative; 47 of the 50 sera scored negative were available for testing by ELISA (RSR/Kronus) and AQP4-transfected cell binding assays (CBA slides [Euroimmun] and in-house fluorescence-activated cell sorting [FACS]). Clinical and demographic characteristics were compared based on final serostatus.

Results RESULTS: Thirty of the 47 IIF-negatives (64%) were re-classified seropositive. Overall, AQP4-IgG detection rate was improved to 88% by FACS assay, 85% by CBA and 80% by ELISA. For 24 of these 30 patients, serial specimens were available. Subsequent sera yielded a positive result in only 2 patients whose initial serum was negative by FACS assay: the 4th of 6 specimens in one, and the subsequent 3 in the other. Of the 17 cases finally scored seronegative, only one specimen was available for 7, and 14 were receiving immunotherapy when blood was drawn. By comparison with seropositive cases, sexes were equally represented in seronegatives (female:male = 8:1 in seropositives; p<0.0001); simultaneous optic neuritis and transverse myelitis at disease onset was 10-fold more frequent in seronegatives (29% versus 3%, p=0.0001).

Conclusions CONCLUSIONS: Serological tests employing recombinant AQP4 antigen are significantly more sensitive than tissue-based IIF for NMO-IgG detection. Initial testing should be done before commencing immunotherapy and, if negative, a subsequent specimen tested. Patients seronegative by most sensitive (FACS) assay differ phenotypically from AQP4-IgG-seropositive patients.

Authors/Disclosures
Yujuan Jiao PRESENTER	No disclosure on file
	No disclosure on file
Vanda Lennon, MD, PhD (Mayo Clinic)	The institution of Dr. Lennon has received research support from NIH. Dr. Lennon has received intellectual property interests from a discovery or technology relating to health care.
Amy M. Quek, MBBS (National University Hospital)	The institution of Dr. Quek has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Dr. Quek has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Quek has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astra Zeneca. The institution of Dr. Quek has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. The institution of Dr. Quek has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. The institution of Dr. Quek has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Astra Zeneca.
Andrew McKeon, MD (Mayo Clinic)	The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
Chiara Costanzi	No disclosure on file
	No disclosure on file
Raffaele Iorio, MD (Catholic University)	Dr. Iorio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Iorio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Iorio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Iorio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dianthus Therapeutics. Dr. Iorio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Johnson. Dr. Iorio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Iorio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Iorio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx. Dr. Iorio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Johnson&Johnson.
	No disclosure on file
	No disclosure on file
Brian G. Weinshenker, MD, FAAN (University of Virginia Health System)	Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CANbridge Pharmaceuticals. Dr. Weinshenker has received personal compensation in the range of $0-$499 for serving as a Consultant for CALIBR. Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Weinshenker 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. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Group (Chugai, Genentech, Roche). Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharmaceuticals. Dr. Weinshenker has received research support from Guthy Jackson Charitable Foundation. Dr. Weinshenker has received intellectual property interests from a discovery or technology relating to health care.
Dean M. Wingerchuk, MD, FAAN (Mayo Clinic)	Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Wingerchuk 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. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Wingerchuk 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. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Meyer Squibb. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Wingerchuk has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca. Dr. Wingerchuk 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. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abcuro. Dr. Wingerchuk 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 Wolters Kluwers.
Elizabeth A. Shuster, MD	No disclosure on file
Claudia F. Lucchinetti, MD, FAAN (University of De Medical School, Health Learning Blg)	The institution of Dr. Lucchinetti has received research support from Biogen Idec. The institution of Dr. Lucchinetti has received research support from NIH/NINDS. The institution of Dr. Lucchinetti has received research support from National Institute of Neurological Disorders and Stroke . The institution of Dr. Lucchinetti has received research support from National Multiple Sclerosis Society. The institution of Dr. Lucchinetti has received research support from National Center for Advancing Translational Sciences. Dr. Lucchinetti has received intellectual property interests from a discovery or technology relating to health care. Dr. Lucchinetti has a non-compensated relationship as a Member with National Institute of Neurological Disorders that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Board of Directors, Association of University Professors of Neurology that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Trustees that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Governors that is relevant to AAN interests or activities.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. 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 personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. 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 Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. 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. Dr. Pittock has received publishing royalties from a publication relating to health care.

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