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Ofatumumab therapy modulates the meningeal lymphatic draining function in patients with multiple sclerosis: a pilot
Shu Yang1, Xiu-Wei Fu2, Zhi-Xuan Liu2
1Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Background And Objectives:
Meningeal lymphatic vessels (mLVs) are critical for central nervous system waste clearance and immunomodulation， implicated in multiple sclerosis pathogenesis. Although ofatumumab is effective in treating relapsing-remitting MS (RRMS), its effects on mLVs function remain unclear. This study aimed to investigate its impact on mLVs drainage in RRMS patients.
Methods:
Fifteen RRMS patients were enrolled in this prospective cohort study with ofatumumab, and nine healthy controls were recruited. Drainage function of mLVs was quantified via dynamic contrast-enhanced magnetic resonance imaging at baseline, month 6 and month 12. Correlations between changes in drainage function and immune cell subsets were analyzed.
Results:
Following ofatumumab treatment, significant reductions were observed in mean time-to-peak (0.75 to 0.52, p = 0.007) and area under the curve (AUC, 30.70 to 12.67, p = 0.001) within mLVs. Baseline mLVs parameters did not differ between RRMS patients and healthy controls. Change of AUC (ΔAUC) was positively associated with regulatory T cell frequency (ΔTreg, r = 0.539, p = 0.038) and negatively associated with central memory CD4+ T cells (ΔTCM, r = -0.535, p = 0.040). Symbol Digit Modalities Test scores were negatively associated with TTP at baseline (r = -0.535, p = 0.040), whereas no correlations were observed between changes in mLVs parameters and clinical outcomes (all p > 0.05).
Conclusion:
Ofatumumab improved mLVs drainage in RRMS and was associated with a shift toward regulatory T cell phenotype. These findings suggest that modulation of meningeal lymphatics may contribute to the immunomodulatory effects of anti-CD20 therapy.
Insights
Ofatumumab treatment improved meningeal lymphatic vessels (mLVs) drainage in multiple sclerosis patients. This enhancement correlated with increased regulatory T cells, suggesting a role for mLVs modulation in anti-CD20 therapy effects.
Area of Science:
- Neuroimmunology
- Central Nervous System (CNS) Physiology
- Lymphatic System Research
Background:
- Meningeal lymphatic vessels (mLVs) are crucial for CNS waste removal and immune regulation, playing a role in multiple sclerosis (MS) pathogenesis.
- Ofatumumab is an effective treatment for relapsing-remitting MS (RRMS), but its impact on mLVs function is not well understood.
Purpose of the Study:
- To investigate the effect of ofatumumab on mLVs drainage function in RRMS patients.
- To explore the relationship between changes in mLVs function and immune cell subsets following ofatumumab treatment.
Main Methods:
- A prospective cohort study involving 15 RRMS patients treated with ofatumumab and 9 healthy controls.
- Quantification of mLVs drainage using dynamic contrast-enhanced MRI at baseline, 6 months, and 12 months.
- Analysis of correlations between mLVs drainage parameters and immune cell subsets, including regulatory T cells (Tregs) and central memory CD4+ T cells (TCM).
Main Results:
- Ofatumumab treatment led to significant improvements in mLVs drainage, indicated by reduced time-to-peak (TTP) and area under the curve (AUC).
- Baseline mLVs parameters were comparable between RRMS patients and healthy controls.
- Improved drainage (ΔAUC) was positively associated with increased Tregs and negatively associated with TCM frequency. No significant correlation was found between changes in mLVs parameters and clinical outcomes.
Conclusions:
- Ofatumumab enhances mLVs drainage function in RRMS patients.
- The observed improvement in mLVs drainage is linked to a shift towards a regulatory T cell phenotype.
- These findings suggest that modulating meningeal lymphatics may be a mechanism underlying the immunomodulatory effects of anti-CD20 therapies like ofatumumab.
