Topic/Product:
CNS, CNS Disease Panel 120, MOGAD
- June 23, 2026
Disease Area:
CNS
Sample Type:
CSF
Abstract
Abstract
Background and Objectives
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder that overlaps clinically with multiple sclerosis (MS) but immunopatho-
logically distinct. Although often considered an acute inflammatory disease, recurrent attacks in MOGAD can lead to demyelination, axonal injury, and secondary neurodegeneration. Reliable biomarkers associated with relapse risk and disease subphenotypes, including optic neuritis, remain limited. Here, we aimed to define molecular and cellular signatures that distinguish MOGAD from MS as a prototypical neuroinflammatory disease and from Alzheimer disease (AD) as a proxy of neurodegeneration and to identify candidate immune–proteomic features associated with relapse frequency and clinical phenotype in MOGAD.
Methods
CSF, serum, and whole-blood samples from patients with MOGAD (n = 67), MS (n = 49), and AD (n = 36) were profiled using NULISAseq™ CSF proteomics, Olink Explore 3072 CSF and serum proteomics, and high-dimensional mass cytometry for immune cell characterization. In MOGAD, longitudinal clinical data, including total attack counts from the earliest documented attack through follow-up, were integrated with immune and proteomic profiles to assess associations with disease course and clinical phenotype.
Results
CSF and blood proteomic profiling revealed distinct inflammatory and cardiometabolic proteomic profiles in MOGAD, differentiating it from both MS and AD. Compared with MS, MOGAD showed relative reductions in lymphocyte populations with regulatory phenotypes. Within MOGAD, re-
lapsing disease was associated with reduced frequencies of CD8 + CCR7 + CD31 + CTLA4 + T cells and concurrent expansion of double-negative γδ T-cell subsets. IL-13 correlated positively with relapse frequency and inversely with circulating regulatory T cells, whereas IL-32 and CASP4 showed opposite associations, correlating negatively with relapse count and positively with Treg frequency. IL-13 was also inversely associated with CD31-expressing CD8 + T cells. Phenotype-stratified analyses suggested that these immune-proteomic relationships differed according to clinical pre-
sentation, including optic neuritis vs nonoptic neuritis phenotypes.
Authors & Affiliations
Gerardina Gallaccio, 1,2,3, * Anna M¨ uller,1,2,3, * Meng Wang, 1,2,3 Lisa-Marie Diekmann, 1,2,3 Carolin Otto, 4 Alessandro Dinoto, 5 Vanessa Chiodega, 5 Carolin Schwake, 6 Sven Jarius, 7 Tatiana Usnich, 8 Pia Sophie Sperber, 4 Lina Anderhalten, 8 Tatchaporn Ongphichetmetha, 9 Angus Byars, 10 Deni Subasic, 10 Desiree Kunkel, 11
Ilya Ayzenberg, 6 Sara Mariotto, 5 Sara Samadzadeh, 1,2,3,† Friedemann Paul, 1,2,3,4,8,† and Chotima B
¨ottcher
1,2,3,†
1 Experimental and Clinical Research Center, a cooperation between the Max Delbr¨ uck Center for Molecular Medicine in the Helmholtz Association and Charit ´ e Universit ¨ atsmedizin
Berlin, Germany; 2 Charit ´ e—Universit ¨ atsmedizin Berlin, corporate member of Freie Universit ¨ at Berlin and Humboldt-Universit ¨ at zu Berlin, Germany; 3 Max Delbr¨ uckCenter for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; 4 Department of Neurology with Experimental Neurology, Charit ´ e—Universit ¨ atsmedizin Berlin, corporate member of Freie Universit ¨ at Berlin and Humboldt-Universit ¨ at zu Berlin, Germany; 5 Neurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy; 6 Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Germany; 7 Division of Neuroimmunology, Department of Neurology, University of Heidelberg, Germany; 8 Neuroscience Clinical Research Center, Charit ´ e—Universit ¨ atsmedizin Berlin, corporate member of Freie Universit ¨ at Berlin and Humboldt-Universit ¨ at zu Berlin, Germany;
9 Siriraj Neuroimmunology Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 10 F. Hoffmann-La Roche Ltd. (A.B., D.S.), Basel, Switzerland; and 11 Flow & Mass Cytometry Core Facility, Berlin Institute of Health at Charit ´ e – Universit ¨ atsmedizin Berlin, Germany.