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Abstract Details

Aquaporin-4 Antibody Isoform Binding Specificity Does Not Explain Clinical Variations in Neuromyelitis Optica
MS and Related Diseases
P02 - (-)
137
BACKGROUND: The two most abundantly expressed aquaporin-4 isoforms in humans are M1 and M23. M23 clusters at the cell surface, which may enhance antibody binding and complement activation. Others have demonstrated differences in the relative binding to the two isoforms in NMO/NMO spectrum disorder patients' sera. The clinical significance of this is unknown.
DESIGN/METHODS: M23 and M1 aquaporin-4 antibody end-point dilution titers were determined retrospectively in 47 remission samples and 19 relapse samples from 33 clinically well-characterized NMO/NMOSD patients seen in a UK specialist NMO center. Titers were measured using flow cytometry of HEK cells stably transfected with either the M23 or the M1 isoform.
RESULTS: M1 antibodies were detectable in 18/19 relapse and 33/47 remission samples whilst M23 antibodies were undetectable in only 2 remission samples. M23 titers were higher than M1 titers in 64/66 samples; two samples had equal titers. Samples were measured longitudinally in 14 patients; M1 antibodies became undetectable in 4/14 patients after treatment whilst M23 antibodies were still detected in all but one but at lower levels. Over time, changes in M23 and M1 titers within a patient tended to occur in parallel. Both mean M23 and M1 titers were significantly higher during relapse than in remission (M23: 13690 vs. 5216; M1: 2931 vs. 938). The ratio of M23 to M1 titers varied between patients (range 192:1 to 1:1) but was not related to age at disease onset, disease activity or severity or phenotype.
CONCLUSIONS: Relative aquaporin-4 antibody binding to M23 and M1 isoforms differs between patients but we could not identify an association between these differences and the clinical characteristics of disease.
Authors/Disclosures
Joanna Kitley, MD (Wessex Neurological Centre)
PRESENTER 		No disclosure on file
Patrick Waters, PhD (Oxford Autoimmune Neurology Diagnostic Lab - Nuffield Clinical Neurosciences) Dr. Waters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Waters has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UBC. The institution of Dr. Waters has received research support from Guthy-Jackson Charitable Foundation. Dr. Waters has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
No disclosure on file
Bradford Dickerson, MD, FAAN Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arkuda. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lantheus. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Dickerson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arkuda. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Dickerson has received publishing royalties from a publication relating to health care. Dr. Dickerson has received publishing royalties from a publication relating to health care.
Jacqueline Palace (John Radcliff Hospital Oxford Univeristy Hospitals Trust) Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono, Medimmune, Argenx, Janssen, AMgen, UCB, Roche, Novartis, Amplo, Alexion, . Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx, Sanofi. Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Roche, UCB, Alexion, Amgen. Dr. Palace has or had stock in Astra Zenica. The institution of Dr. Palace has received research support from Roche, AMPLO, Alexion, UCB,. argenx, amgen. Dr. Palace has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file