Peer-reviewedCC BY-NC-ND 4.0Annals of Clinical and Translational Neurology
Frequency and Phenotype of Coexisting Aquaporin‐4 and Autoimmune Encephalitis Autoantibodies
15 affiliations
- 1Department of Neurology Mayo Clinic Rochester Minnesota USA
- 2Center for MS and Autoimmune Neurology Mayo Clinic Rochester Minnesota USA
- 3Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA
- 4UAB Department of Neurology University of Alabama at Birmingham School of Medicine Birmingham Alabama USA
- 5Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles Los Angeles California USA
- 6Department of Neurology Keck School of Medicine at the University of Southern California Los Angeles California USA
- 7Division of Hematology/Oncology, Cancer and Blood Disorders Center Stanford Medicine, Valley Children's Healthcare Madera California USA
- 8OhioHealth Multiple Sclerosis Center Riverside Methodist Hospital Columbus Ohio USA
- 9Division of Neurology, Department of Medicine, Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore
- 10Department of Neurological Sciences Rush University Medical Center Chicago Illinois USA
- 11Department of Neurology University of Michigan Ann Arbor Michigan USA
- 12Department of Neurology University of California San Francisco San Francisco California USA
- 13Department of Ophthalmology Mayo Clinic Rochester Minnesota USA
- 14Departments of Neurology and Neuroscience Mayo Clinic Jacksonville Florida USA
- 15Department of Neurology, Mellen Centre for Multiple Sclerosis and Autoimmune Neurology Cleveland Clinic Cleveland Ohio USA
Abstract
Among 9457 aquaporin‐4 (AQP4) immunoglobulin G‐positive patients, 2071 underwent autoimmune encephalitis antibody testing and 85 (4%) had coexisting antibodies, most commonly cerebrospinal fluid glial fibrillary acidic protein‐IgG and N‐methyl‐D‐aspartate receptor‐IgG, or serum high‐titer GAD65‐IgG. Compared with AQP4‐IgG positive neuromyelitis optica spectrum disorder controls, dual‐positive patients were younger and more frequently exhibited encephalopathy, psychiatric symptoms, seizures, ovarian teratomas, and deep gray matter, temporal lobe, or diencephalic MRI abnormalities. GAD65‐IgG‐positive patients developed stiff‐person syndrome. These findings define a distinct mixed glial‐neuronal autoimmune phenotype and support additional neural antibody testing in atypical AQP4‐IgG‐positive presentations.
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BibTeX
@article{cacciaguerra2026frequency,
title = {{Frequency and Phenotype of Coexisting Aquaporin‐4 and Autoimmune Encephalitis Autoantibodies}},
author = {Laura Cacciaguerra and Binxia Yang and Vanda A. Lennon and Shruti P. Agnihotri and Nusrat Ahsan and Karen S. Fernandez and Erin McLeod and Georgios Mangioris and William R. Meador and Wendy G. Mitchell and Jacqueline A. Nicholas and Amy M. L. Quek and Thomas Shoemaker and Kurt Sieloff and Matt C. Edmond and Rebekah A. Laggis and Kristin L. Flynn and Jessica A. Sagen and Emmanuelle Waubant and John J. Chen and Sarosh R. Irani and Andrew McKeon and Anastasia Zekeridou and Eoin P. Flanagan and Sean J. Pittock and Amy Kunchok},
journal = {Annals of Clinical and Translational Neurology},
year = {2026},
month = nov,
doi = {10.1002/acn3.70541},
url = {https://doi.org/10.1002/acn3.70541},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Frequency and Phenotype of Coexisting Aquaporin‐4 and Autoimmune Encephalitis Autoantibodies
AU - Laura Cacciaguerra
AU - Binxia Yang
AU - Vanda A. Lennon
AU - Shruti P. Agnihotri
AU - Nusrat Ahsan
AU - Karen S. Fernandez
AU - Erin McLeod
AU - Georgios Mangioris
AU - William R. Meador
AU - Wendy G. Mitchell
AU - Jacqueline A. Nicholas
AU - Amy M. L. Quek
AU - Thomas Shoemaker
AU - Kurt Sieloff
AU - Matt C. Edmond
AU - Rebekah A. Laggis
AU - Kristin L. Flynn
AU - Jessica A. Sagen
AU - Emmanuelle Waubant
AU - John J. Chen
AU - Sarosh R. Irani
AU - Andrew McKeon
AU - Anastasia Zekeridou
AU - Eoin P. Flanagan
AU - Sean J. Pittock
AU - Amy Kunchok
PY - 2026
DA - 2026/11/04
JO - Annals of Clinical and Translational Neurology
DO - 10.1002/acn3.70541
UR - https://doi.org/10.1002/acn3.70541
AB - Among 9457 aquaporin‐4 (AQP4) immunoglobulin G‐positive patients, 2071 underwent autoimmune encephalitis antibody testing and 85 (4%) had coexisting antibodies, most commonly cerebrospinal fluid glial fibrillary acidic protein‐IgG and N‐methyl‐D‐aspartate receptor‐IgG, or serum high‐titer GAD65‐IgG. Compared with AQP4‐IgG positive neuromyelitis optica spectrum disorder controls, dual‐positive patients were younger and more frequently exhibited encephalopathy, psychiatric symptoms, seizures, ovarian teratomas, and deep gray matter, temporal lobe, or diencephalic MRI abnormalities. GAD65‐IgG‐positive patients developed stiff‐person syndrome. These findings define a distinct mixed glial‐neuronal autoimmune phenotype and support additional neural antibody testing in atypical AQP4‐IgG‐positive presentations.
SN - 2328-9503
ER -