Serum and CSF cytokine profile impact clinical phenotype in pediatric MOGAD

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has a broad spectrum of clinical phenotypes, including acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM), and cerebral cortical encephalitis (CCE). Although these conditions exhibit diverse outcomes and require different treatment options for relapse prevention, no biomarkers have been identified to distinguish the clinical phenotypes. This study aimed to investigate the properties of cytokines and chemokines in the serum and cerebrospinal fluid (CSF) of patients with MOGAD and to determine whether they are associated with the clinical phenotype. In this retrospective cohort study, we analyzed cytokines and chemokines in paired serum and CSF samples obtained during the acute phase before treatment from patients with MOG-IgG positivity, classified into five clinical phenotypes (ADEM, CCE, ON, TM, and “others”). Of the 50 patients diagnosed with MOGAD, 19 (38%) were diagnosed with ADEM, 9 (18%) with CCE, 3 (6%) with ON + TM, 9 (18%) with ON, and 10 (20%) with others. Overall, the CSF levels of Th17-related (including IL-6, CXCL8, G-CSF, IL-17, and IL-21) and B cell-related (including CXCL13, BAFF, and APRIL) cytokines/chemokines were elevated in pediatric patients with MOGAD compared with non-inflammatory neurological disease controls. Phenotype-stratified analyses of ADEM, CCE, and ON demonstrated higher CSF IL-6 and CXCL8 levels in encephalitic phenotypes (ADEM/CCE) than in ON. By contrast, no significant difference in the CSF-to-serum ratio (C/S ratio) for each cytokine was observed among the three phenotypes. Only the CXCL13 C/S ratio correlated with the ΔMOG-IgG C/S ratio. Pediatric patients with MOGAD showed limited phenotype-specific heterogeneity in their cytokine/chemokine profiles. Nevertheless, leptomeningeal inflammation was more prominent in patients with encephalitic presentations. Additionally, intrathecal MOG-IgG synthesis may be linked to intracranial inflammatory activity, which could inform future prospective studies using stratified treatment approaches.