Abstract Details

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

Topic Autoimmune Neurology

Presentation(s) P2 - Poster Session 02 (3:00 PM-4:00 PM)

Poster/Presentation
Number 1-029

Objective

To 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.

Background

MOGAD 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/Methods

We 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.

Results

Seventy-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.

Conclusions

CSF 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.

Authors/Disclosures
Georgios Mangioris, MD PRESENTER	Dr. Mangioris has nothing to disclose.
Binxia Yang (Mayo clinic)	Binxia Yang has nothing to disclose.
Yahel Segal, MD (Mayo Clinic)	Dr. Segal has nothing to disclose.
Kai Guo, MD, PhD	Dr. Guo has nothing to disclose.
Laura Cacciaguerra, MD, PhD (Mayo Clinic)	Dr. Cacciaguerra has nothing to disclose.
Nisa Vorasoot, MD	Dr. Vorasoot has nothing to disclose.
Jan-Mendelt Tillema, MD (Mayo Clinic)	Dr. Tillema has nothing to disclose.
John Chen	John Chen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. John Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. John Chen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB.
Divyanshu Dubey, MD, FAAN (Mayo Clinic)	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.
Andrew McKeon, MD (Mayo Clinic)	The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
John R. Mills, MD, PhD (Mayo Clinic)	The institution of Dr. Mills has received research support from Werfen Diagnostics. Dr. Mills has received intellectual property interests from a discovery or technology relating to health care.
Michel Toledano, MD (Mayo Clinic)	Dr. Toledano has nothing to disclose.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic)	The institution of Dr. Flanagan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Merck. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received intellectual property interests from a discovery or technology relating to health care. Dr. Flanagan has received intellectual property interests from a discovery or technology relating to health care. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology that is relevant to AAN interests or activities.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic)	The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.

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