TY - JOUR
T1 - MOG and AQP4 Antibodies among Children with Multiple Sclerosis and Controls
AU - United States Network of Pediatric Multiple Sclerosis Centers
AU - Gaudioso, Cristina M.
AU - Mar, Soe
AU - Casper, T. Charles
AU - Codden, Rachel
AU - Nguyen, Adam
AU - Aaen, Gregory
AU - Benson, Leslie
AU - Chitnis, Tanuja
AU - Francisco, Carla
AU - Gorman, Mark P.
AU - Goyal, Manu S.
AU - Graves, Jennifer
AU - Greenberg, Benjamin M.
AU - Hart, Janace
AU - Krupp, Lauren
AU - Lotze, Timothy
AU - Narula, Sona
AU - Pittock, Sean J.
AU - Rensel, Mary
AU - Rodriguez, Moses
AU - Rose, John
AU - Schreiner, Teri
AU - Tillema, Jan Mendelt
AU - Waldman, Amy
AU - Weinstock-Guttman, Bianca
AU - Wheeler, Yolanda
AU - Waubant, Emmanuelle
AU - Flanagan, Eoin P.
N1 - Funding Information:
The authors thank Jessica Sagen for her assistance with the study coordination. We also thank the patients and families who participated in the study. This study was funded by the National Multiple Sclerosis Society and National Institute of Neurological Disorders and Stroke (R01NS113828, 1R01NS071463, and S1‐1808‐32326).
Publisher Copyright:
© 2022 American Neurological Association.
PY - 2023/2
Y1 - 2023/2
N2 - Objective: The purpose of this study was to determine the frequency of myelin oligodendrocyte glycoprotein (MOG)-IgG and aquaporin-4 (AQP4)-IgG among patients with pediatric-onset multiple sclerosis (POMS) and healthy controls, to determine whether seropositive cases fulfilled their respective diagnostic criteria, to compare characteristics and outcomes in children with POMS versus MOG-IgG-associated disease (MOGAD), and identify clinical features associated with final diagnosis. Methods: Patients with POMS and healthy controls were enrolled at 14 US sites through a prospective case–control study on POMS risk factors. Serum AQP4-IgG and MOG-IgG were assessed using live cell-based assays. Results: AQP4-IgG was negative among all 1,196 participants, 493 with POMS and 703 healthy controls. MOG-IgG was positive in 30 of 493 cases (6%) and zero controls. Twenty-five of 30 patients positive with MOG-IgG (83%) had MOGAD, whereas 5 of 30 (17%) maintained a diagnosis of multiple sclerosis (MS) on re-review of records. MOGAD cases were more commonly in female patients (21/25 [84%] vs 301/468 [64%]; p = 0.044), younger age (mean = 8.2 ± 4.2 vs 14.7 ± 2.6 years; p < 0.001), more commonly had initial optic nerve symptoms (16/25 [64%] vs 129/391 [33%]; p = 0.002), or acute disseminated encephalomyelitis (ADEM; 8/25 [32%] vs 9/468 [2%]; p < 0.001), and less commonly had initial spinal cord symptoms (3/20 [15%] vs 194/381 [51%]; p = 0.002), serum Epstein–Barr virus (EBV) positivity (11/25 [44%] vs 445/468 [95%]; p < 0.001), or cerebrospinal fluid oligoclonal bands (5/25 [20%] vs 243/352 [69%]; p < 0.001). Interpretation: MOG-IgG and AQP4-IgG were not identified among healthy controls confirming their high specificity for pediatric central nervous system (CNS) demyelinating disease. Five percent of those with prior POMS diagnoses ultimately had MOGAD; and none had AQP4-IgG positivity. Clinical features associated with a final diagnosis of MOGAD in those with suspected MS included initial ADEM phenotype, younger age at disease onset, and lack of EBV exposure. ANN NEUROL 2023;93:271–284.
AB - Objective: The purpose of this study was to determine the frequency of myelin oligodendrocyte glycoprotein (MOG)-IgG and aquaporin-4 (AQP4)-IgG among patients with pediatric-onset multiple sclerosis (POMS) and healthy controls, to determine whether seropositive cases fulfilled their respective diagnostic criteria, to compare characteristics and outcomes in children with POMS versus MOG-IgG-associated disease (MOGAD), and identify clinical features associated with final diagnosis. Methods: Patients with POMS and healthy controls were enrolled at 14 US sites through a prospective case–control study on POMS risk factors. Serum AQP4-IgG and MOG-IgG were assessed using live cell-based assays. Results: AQP4-IgG was negative among all 1,196 participants, 493 with POMS and 703 healthy controls. MOG-IgG was positive in 30 of 493 cases (6%) and zero controls. Twenty-five of 30 patients positive with MOG-IgG (83%) had MOGAD, whereas 5 of 30 (17%) maintained a diagnosis of multiple sclerosis (MS) on re-review of records. MOGAD cases were more commonly in female patients (21/25 [84%] vs 301/468 [64%]; p = 0.044), younger age (mean = 8.2 ± 4.2 vs 14.7 ± 2.6 years; p < 0.001), more commonly had initial optic nerve symptoms (16/25 [64%] vs 129/391 [33%]; p = 0.002), or acute disseminated encephalomyelitis (ADEM; 8/25 [32%] vs 9/468 [2%]; p < 0.001), and less commonly had initial spinal cord symptoms (3/20 [15%] vs 194/381 [51%]; p = 0.002), serum Epstein–Barr virus (EBV) positivity (11/25 [44%] vs 445/468 [95%]; p < 0.001), or cerebrospinal fluid oligoclonal bands (5/25 [20%] vs 243/352 [69%]; p < 0.001). Interpretation: MOG-IgG and AQP4-IgG were not identified among healthy controls confirming their high specificity for pediatric central nervous system (CNS) demyelinating disease. Five percent of those with prior POMS diagnoses ultimately had MOGAD; and none had AQP4-IgG positivity. Clinical features associated with a final diagnosis of MOGAD in those with suspected MS included initial ADEM phenotype, younger age at disease onset, and lack of EBV exposure. ANN NEUROL 2023;93:271–284.
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U2 - 10.1002/ana.26502
DO - 10.1002/ana.26502
M3 - Article
C2 - 36088544
AN - SCOPUS:85139188761
SN - 0364-5134
VL - 93
SP - 271
EP - 284
JO - Annals of neurology
JF - Annals of neurology
IS - 2
ER -