TY - JOUR
T1 - MOG-IgG1 and co-existence of neuronal autoantibodies
AU - Kunchok, Amy
AU - Flanagan, Eoin P.
AU - Krecke, Karl N.
AU - Chen, John J.
AU - Caceres, J. Alfredo
AU - Dominick, Justin
AU - Ferguson, Ian
AU - Kinkel, Revere
AU - Probasco, John C.
AU - Ruvalcaba, Miguel
AU - Santoro, Jonathan D.
AU - Sieloff, Kurt
AU - Timothy, Jeremy
AU - Weinshenker, Brian G.
AU - McKeon, Andrew
AU - Pittock, Sean J.
N1 - Funding Information:
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Amy Kunchok has received research support from Biogen in previous employment. Eoin P. Flanagan is a site principal investigator in a randomized placebo-controlled clinical trial of Inebilizumab (A CD19 inhibitor) in neuromyelitis optica spectrum disorders funded by MedImmune/Viela Bio. He receives no personal compensation and just receives reimbursement for the research activities related to the trial. Karl. N. Krecke, John J. Chen, J. Alfredo Caceres, Justin Dominick, Ian Ferguson, Revere Kinkel, John C. Probasco, Miguel Ruvalcaba, Kurt Sieloff, and Jeremy Timothy report no disclosures. Jonathan D. Santoro receives honoraria through GLG consulting and has received grant funding through the National Multiple Sclerosis Society. Brian G. Weinshenker receives royalties from RSR Ltd, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for NMO and related disorders, served on adjudication committee for clinical trials in NMO conducted by MedImmune and Alexion, and consulted for Chugai and Mitsubishi Tanabe regarding clinical trials for NMO. Andrew McKeon has patent applications pending for the following IgGs as biomarkers of autoimmune neurological disease: Septin-5 and MAP1B. He has consulted for Grifols, Medimmune, and Euroimmun, and received research support from Grifols, Medimmune, Alexion, and Euroimmun but has not received personal compensation. Sean J. Pittock reports grants, personal fees, and non-financial support from Alexion Pharmaceuticals, Inc.; grants from Grifols, Autoimmune Encephalitis Alliance; grants, personal fees, non-financial support, and other from MedImmune, Inc. He has a patent# 9,891,219 (Application#12-573942) “Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive.”
Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the NIH National Institute of Neurological Disorders and Stroke (Grant No. R01NS113828).
Funding Information:
The authors would like to thank Dr Ilya Kister from New York University Lagone, who provided clinical data for a patient. They would like to thank and acknowledge their administrative and coordinator staff Ms Mary Curtis, Ms Sara Vinje, Ms Jessica Sagen, Ms Katie Doane, and Ms Cara Thomas. They would also like to thank their neuroimmunology laboratory technical staff Mr John Schmeling, Ms Nancy Peters, and Ms Vickie Mewhorter. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the NIH National Institute of Neurological Disorders and Stroke (Grant No. R01NS113828).
Publisher Copyright:
© The Author(s), 2020.
PY - 2021/7
Y1 - 2021/7
N2 - Background: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood. Objectives: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients. Methods: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG. Results: A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2–39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy (p = 0.001), seizures (p = 0.045), and leptomeningeal enhancement (p = 0.045). Conclusion: NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.
AB - Background: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood. Objectives: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients. Methods: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG. Results: A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2–39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy (p = 0.001), seizures (p = 0.045), and leptomeningeal enhancement (p = 0.045). Conclusion: NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.
KW - MOG-IgG1
KW - NMDA-R-IgG
KW - autoimmune encephalitis
KW - biomarkers
KW - demyelination
KW - neuronal antibodies
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U2 - 10.1177/1352458520951046
DO - 10.1177/1352458520951046
M3 - Article
C2 - 32907470
AN - SCOPUS:85090581165
SN - 1352-4585
VL - 27
SP - 1175
EP - 1186
JO - Multiple Sclerosis
JF - Multiple Sclerosis
IS - 8
ER -