MOG Antibody-associated Disease (MOGAD) CSF Biomarkers Reveal Distinct Signatures from Relapsing-remitting Multiple Sclerosis

ObjectiveTo characterize immune and neural injury biomarkers in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare them to relapsing–remitting multiple sclerosis (RRMS), aquaporin-4(AQP4)-IgG-positive, and non-inflammatory controls. BackgroundMOGAD is a CNS demyelinating disorder with unclear pathogenesis and no proven treatment. Histopathological studies demonstrate predominant CD4+ T-cell infiltration, with contributions from macrophages, microglia, and granulocytes; however, their roles in disease development remain incompletely understood. Data on CSF cytokines/chemokines, neurofilament light (NfL), and sTREM2 in MOGAD are scant. Design/MethodsWe measured IL-1-beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17A, BAFF, IL-8/CXCL8, CXCL9, CXCL10, CXCL13, GM-CSF, IFN-gamma, TNF-alpha, NfL, and sTREM2 using the ELLA multiplexed automated immunoassay in CSF and paired sera of: (1) MOGAD patients sampled within one month of an attack (09/2011-10/2023), and (2) a laboratory-based cohort of patients with MOG-IgG titers ≥1:1000 (reference <1:20; 05/2018-03/2024). RRMS, AQP4-IgG-positive patients, and non-inflammatory controls served as comparators. ResultsSeventy-four MOG-IgG–positive patients with available CSF were included (median age, 25 years [range, 5–76]; 45 [61%] female); 47 had paired sera. Among 24 with clinical data, 15 (63%) had not received attack treatment prior to sampling. CSF from 26 RRMS, 84 AQP4-IgG-positive, and 42 non-inflammatory controls were analyzed. Compared with non-inflammatory controls, MOG-IgG-positive patients exhibited higher CSF concentrations of IL-1-beta, IL-6, IL-8/CXCL8, IL-10, IL-17A, CXCL13, and GM-CSF, and higher serum concentrations of IL-1-beta, IL-6, IL-17A, and GM-CSF (P<0.05). Compared with AQP4-IgG–positive patients, they had higher CSF IL-1-beta, IL-5, IL-6, IL-10, IL-17A, GM-CSF, and TNF-alpha, and lower NfL (P≤0.02). Compared with RRMS, they showed higher CSF IL-6 and IL-17A, and lower CSF IFN-gamma, sTREM2, and NfL (P≤0.03); CSF IL-6 and sTREM2 best discriminated MOGAD from RRMS. ConclusionsCSF immune profiles in MOGAD indicate a Th17-skewed immune response and suggest potential therapeutic targets. CSF IL-6 and sTREM2 may aid in distinguishing MOGAD from RRMS.