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Article

Live Cell-Based Semi-Quantitative Stratification Highlights Titre-Dependent Phenotypic Heterogeneity in MOGAD: A Single-Centre Experience

by
Donato Regina
,
Concetta Domenica Gargano
,
Tommaso Guerra
,
Antonio Frigeri
,
Damiano Paolicelli
,
Maddalena Ruggieri
and
Pietro Iaffaldano
*,†
Department of Translational Biomedicines and Neurosciences (DiBraiN), University of Bari “Aldo Moro”, 70124 Bari, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(19), 9615; https://doi.org/10.3390/ijms26199615
Submission received: 7 August 2025 / Revised: 23 September 2025 / Accepted: 30 September 2025 / Published: 1 October 2025
(This article belongs to the Special Issue Multiple Sclerosis: The Latest Developments in Immunology and Therapy)

Abstract

Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is an inflammatory demyelinating disorder of the central nervous system characterised by heterogeneous clinical and radiological presentations. Accurate interpretation of serum anti–myelin oligodendrocyte glycoprotein (anti-MOG) antibody titres is critical to improve diagnostic precision and prognostic assessment. This single-centre retrospective study evaluated 19 patients diagnosed with MOGAD in 2023, all of whom were seropositive for anti-MOG IgG, as confirmed by live cell-based assays (CBAs) using full-length human MOG and IgG1-specific secondary antibodies. Antibody quantification combined a ratiometric semi-quantitative fluorescence index with classical endpoint dilution titres, enabling classification into low, medium, and high titre groups. Stratification revealed titre-dependent phenotypic heterogeneity: high-titre patients were older at onset and predominantly presented with optic neuritis, often bilateral, and encephalic involvement, whereas low-titre patients more frequently exhibited spinal cord syndromes, cerebellar or brainstem symptoms, and a higher prevalence of cerebrospinal fluid-restricted oligoclonal bands. Semi-quantitative fluorescence ratios correlated consistently with endpoint titres, and exponential decay analysis demonstrated slower signal loss in high-titre sera, confirming assay reliability. No significant association emerged between titre level and monophasic versus relapsing disease course. Anti-MOG antibody titres could serve not only as a diagnostic biomarker but also to capture clinically relevant immunopathological diversity, supporting a titre-stratified approach to diagnosis and early prognostication. Incorporating semi-quantitative metrics alongside clinical and imaging features may refine the diagnostic algorithm and prevent misclassification of atypical presentations.
Keywords: MOGAD; semi-quantitative fluorescence index; diagnostic biomarker MOGAD; semi-quantitative fluorescence index; diagnostic biomarker

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MDPI and ACS Style

Regina, D.; Gargano, C.D.; Guerra, T.; Frigeri, A.; Paolicelli, D.; Ruggieri, M.; Iaffaldano, P. Live Cell-Based Semi-Quantitative Stratification Highlights Titre-Dependent Phenotypic Heterogeneity in MOGAD: A Single-Centre Experience. Int. J. Mol. Sci. 2025, 26, 9615. https://doi.org/10.3390/ijms26199615

AMA Style

Regina D, Gargano CD, Guerra T, Frigeri A, Paolicelli D, Ruggieri M, Iaffaldano P. Live Cell-Based Semi-Quantitative Stratification Highlights Titre-Dependent Phenotypic Heterogeneity in MOGAD: A Single-Centre Experience. International Journal of Molecular Sciences. 2025; 26(19):9615. https://doi.org/10.3390/ijms26199615

Chicago/Turabian Style

Regina, Donato, Concetta Domenica Gargano, Tommaso Guerra, Antonio Frigeri, Damiano Paolicelli, Maddalena Ruggieri, and Pietro Iaffaldano. 2025. "Live Cell-Based Semi-Quantitative Stratification Highlights Titre-Dependent Phenotypic Heterogeneity in MOGAD: A Single-Centre Experience" International Journal of Molecular Sciences 26, no. 19: 9615. https://doi.org/10.3390/ijms26199615

APA Style

Regina, D., Gargano, C. D., Guerra, T., Frigeri, A., Paolicelli, D., Ruggieri, M., & Iaffaldano, P. (2025). Live Cell-Based Semi-Quantitative Stratification Highlights Titre-Dependent Phenotypic Heterogeneity in MOGAD: A Single-Centre Experience. International Journal of Molecular Sciences, 26(19), 9615. https://doi.org/10.3390/ijms26199615

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