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Peripheral reactive B cells have a dual role in the pathogenesis and diagnosis of multiple sclerosis. These cells deliver myelin autoreactive antibodies to oligodendrocytes, which can also be a diagnostic biomarker in multiple sclerosis.

Multiple sclerosis (MS) is characterized by a pathogenic immune response that involves the production of autoreactive antibodies against the myelin sheath of oligodendrocytes. This is associated with autoreactive B cells in the central nervous system responsible for releasing antibodies. 

This study investigated the role of extracellular vesicles in delivering antibodies from peripheral B cells to oligodendrocytes and mediating demyelination. The study also investigated the function of these antibodies in diagnosing MS. The findings are published in the journal Frontiers in Immunology.

Participant Characteristics

A total of 136 MS patients, 39 healthy controls, and 23 white matter lesion controls were enrolled in the study. Disease activity in the MS patients was evaluated on the basis of T2-enhancing lesions or clinical relapse over a period of one year. The mean ages of the healthy controls, white matter lesion controls, and MS patients were 45.26 ± 13.58, 64.86 ± 12.84, and 43.04 ± 9.36 years, respectively.

Soluble Myelin Antibody Levels in Peripheral Blood and Cerebrospinal Fluid

There were no significant differences in the anti-myelin basic protein (anti-MBP) and anti-myelin oligodendrocyte glycoprotein (anti-MOG) levels in the peripheral blood across healthy controls, white matter lesion controls, and MS patients. Moreover, the levels of these antibodies in the total circulating extracellular vesicles in peripheral blood were not significantly different across the three groups. However, the anti-MOG and anti-MBP antibodies were largely found in peripheral B-cell-derived extracellular vesicles. The levels of anti-MBP and anti-MOG antibodies in the cerebrospinal fluid-derived extracellular vesicles were significantly lower than in blood-derived extracellular vesicles.

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Comparison of Myelin Antibody Expression in Healthy Controls Versus Multiple Sclerosis

Compared to healthy controls, MS patients had significantly higher levels of antibodies in the B-cell-derived extracellular vesicles. The anti-MOG and anti-MBP antibody content in the B-cell-derived extracellular vesicles was positively correlated. The oligodendrocytes in the MS patients were also found to have significantly higher anti-MBP antibody levels in the extracellular vesicles. On the contrary, healthy controls had significantly higher levels of antibodies against albumin.

Role of Myelin Antibodies in Disease Progression and as Diagnostic Biomarkers

The levels of anti-MBP antibodies were similar across naïve and treated MS patients; however, the expression of anti-MBP and anti-MOG antibodies in the B-cell-derived extracellular vesicles was higher in MS patients than in controls. The same held true for antibodies derived from oligodendrocytes. Hence, disease-modifying treatments, including anti-CD20 monoclonal antibodies, did not alter myelin antibody content. 

Similarly, the levels of antibodies in the extracellular vesicles derived from oligodendrocytes and B cells were not significantly different in MS patients with active and stable disease. The anti-MBP and anti-MOG antibodies derived from extracellular vesicles induced a reduction in the myelin markers.

Source:

Torres Iglesias, G., Fernández-Fournier, M., López-Molina, M., Piniella, D., Laso-García, F., Gómez-de Frutos, M. C., Alonso-López, E., Botella, L., Chamorro, B., Sánchez-Velasco, S., Puertas, I., Tallón Barranco, A., Nozal, P., Díez-Tejedor, E., Gutiérrez-Fernández, M., & Otero-Ortega, L. (2023). Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers. Frontiers in immunology, 14, 1224217. https://doi.org/10.3389/fimmu.2023.1224217