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Here, we aimed to reveal immune markers of DMF\u2010associated lymphopenia. This prospective observational study longitudinally assessed 31 individuals with MS by single\u2010cell mass cytometry before and after 12 and 48\u00a0weeks of DMF therapy. Employing a neural network\u2010based representation learning approach, we identified a CCR4\u2010expressing T helper cell population negatively associated with relevant lymphopenia. CCR4\u2010expressing T helper cells represent a candidate prognostic biomarker for the development of relevant lymphopenia in patients undergoing DMF treatment. 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