MOGandAQP4Antibodies among Children with Multiple Sclerosis and Controls

Abstract

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

Comparison of MRI T2-lesion evolution in pediatric MOGAD, NMOSD, and MS

“…This is pertinent because MOG-IgG titers tend to be highest at disease onset, thus when repeat testing is negative, these MRI findings might help discriminate MOGAD from MS with potential treatment implications. Second, low-titer false-positive MOG-IgG results are recognized to occasionally occur in children, 15 and persistence of all or most T2-lesions over time would favor MS over MOGAD and discriminate true- versus false-positive results. 16 It may also inform MRI surveillance strategies in MOGAD.…”

A retrospective study of myelin oligodendrocyte glycoprotein antibody-associated disease from a clinical laboratory perspective

“…The UK cohort ( 15 ) also showed a slight female preponderance of 62%, with an average age of onset of 31 years (range 3–69 years). In a multi-center study ( 16 ) involving at least three US race/ethnicities (white, black, Asian and other), the proportion of women was as high as 85% (21/25). The prevalence of MOGAD varies between men and women in different studies.…”

Short‐chain fatty acid producers in the gut are associated with pediatric multiple sclerosis onset

“…All participants were tested for the presence of myelin oligodendrocyte glycoprotein antibodies at the Mayo Clinic neuroimmunology laboratory (Rochester, MN) using a live cell‐based flow cytometry assay. Those with positive results were excluded and cases with low titers had their final diagnosis ascertained by two MS experts, as previously described 12 . Additionally, individuals exposed to systemic antibiotics, probiotics, or steroids within 30 days before sample collection were excluded.…”

“…Those with positive results were excluded and cases with low titers had their final diagnosis ascertained by two MS experts, as previously described. 12 Additionally, individuals exposed to systemic antibiotics, probiotics, or steroids within 30 days before sample collection were excluded. POMS cases on a disease‐modifying therapy (DMT) were invited to enroll if on stable dosing for more than three months.…”