Abstract Details

Title Frequency and Phenotype of Coexisting AQP4-IgG with Synaptic Autoantibodies in Patients Undergoing Serological Testing for CNS Inflammatory Disease

Topic Autoimmune Neurology

Presentation(s) S16 - Autoimmune Neurological Disorders: Diagnosis, Biomarkers, and Epidemiology (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Objective

To evaluate the frequency and phenotype of coexisting synaptic neuronal and AQP4 autoantibodies.

Background

Aquaporin-4-IgG (AQP4-IgG) is a biomarker for neuromyelitis optica spectrum disorders (NMOSD) while synaptic neuronal antibodies (NMDA-R-IgG, AMPA-R-IgG, CASPR2-IgG, GABA-B-R-IgG and LGI-1-IgG) are associated with autoimmune encephalopathies. Studies evaluating the coexistence of synaptic astrocytic and neuronal autoantibodies are lacking.

Design/Methods

We identified patients tested with clinically-validated assays (01/2012-09/2019) for both AQP4-IgG and neuronal-IgGs in the Mayo Clinic Neuroimmunology Laboratory.

Group 1 included patients tested for AQP4, NMDA-R, AMPA-R, and GABA-B-IgGs. Group 2 included patients tested for AQP4, LGI-1 and CASPR2-IgGs.

Results

Group 1: 6197 patients were tested (4755 adults, 1422 children).

Of the adults, 245 were antibody positive; 234 were single antibody positive (AQP4-IgG [140], NMDA-R-IgG [81], AMPA-R-IgG [5], GABA-B-R-IgG [8]). Ten (4%) were AQP4-IgG and NMDA-R-IgG positive, who were all female patients aged 18-45. Of these ten, a third antibody was detected in 4 (MOG-IgG [1], GFAP-IgG [3]).

One male adult had NMDA-R-IgG and AMPA-R-IgG.

Of the children, 80 were antibody positive; 74 single antibody positive (NMDA-R-IgG [41], AQP4-IgG [33], GABA-B-R-IgG [1]). Six (7.5%) patients (3 female, 3 male) were AQP4-IgG and NMDA-R-IgG positive.

Group 2: 4530 patients were tested (3571 adults and 959 children). Of the adults, 130 were single antibody positive; AQP4-IgG [84], LGI-1-IgG [15], CASPR2-IgG [11]. Of the children, 26 were single antibody positive; AQP4-IgG [24], CASPR2-IgG [2]. None were dual positive.

Clinical data for 11/16 AQP4-IgG and NMDA-R-IgG patients included; encephalopathy/encephalitis [8], myelitis [3], hallucinations [2], hypersomnolence [2], ophthalmoparesis [2], ataxia [2], optic neuritis [2], opsoclonus [1], area postrema syndrome [1]. Ovarian teratoma [2] and cyst [1] were identified in adult females.

Conclusions

NMDA-R-IgG was the only synaptic neuronal antibody which co-existed with AQP4-IgG. This occurred in young patients (80% females) with overlapping phenotypes. Co-existence of AQP4-IgG and NMDA-R-IgG may point to a common immunological pathway.

Authors/Disclosures
Amy Kunchok, MBBS (Cleveland Clinic - Mellen Centre) PRESENTER	Dr. Kunchok 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. Kunchok 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 Journal . Dr. Kunchok 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:Open Access Journal .
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic)	The institution of Dr. Flanagan 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. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan 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. The institution of Dr. Flanagan 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. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from Viela Bio. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities.
John Chen	John Chen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. John Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen.
Divyanshu Dubey, MD, FAAN (Mayo Clinic)	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.
Christopher J. Klein, MD, FAAN (Mayo Clinic)	Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sangamo Therapeutics . Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma.
Daniel H. Lachance, MD, FAAN (Mayo Clinic)	Dr. Lachance has nothing to disclose.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic)	The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
Nusrat Ahsan, MD	Dr. Ahsan has nothing to disclose.
Karen Fernandez	No disclosure on file
	No disclosure on file
Wendy G. Mitchell, MD (Children'S Hospital Los Angeles)	Dr. Mitchell has nothing to disclose.
Kurt M. Sieloff, MD (University of Michigan Health System)	Dr. Sieloff has nothing to disclose.
Huidy Shu, MD, PhD (Hawaii Pacific Health Medical Group)	No disclosure on file
Emmanuelle Waubant, MD, PhD, FAAN (USCF MS Center)	The institution of Dr. Waubant has received research support from NIH. The institution of Dr. Waubant has received research support from NMSS. The institution of Dr. Waubant has received research support from PCORI. The institution of Dr. Waubant has received research support from Race to Erase MS. The institution of Dr. Waubant has received research support from Roche. The institution of Dr. Waubant has received research support from Department of Defense. Dr. Waubant has received publishing royalties from a publication relating to health care.
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.
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.
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 UCB. 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 $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. 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 Arialys. 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. The institution of Dr. Pittock has received research support from Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. 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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