To analyze the long-term effect of dimethyl fumarate (DMF) on the lymphocyte subpopulations of multiple sclerosis (MS) patients and its relationship with the activity of the disease.

The optimal response to DMF is mediated by a shift to antiinflammatory and immunoregulatory profile. In a preliminary study of 22 patients with MS followed for 12 months, we observed that, at 3 months of treatment, patients with "No evidence of disease activity (NEDA)" had a decrease in the Th1-like Th17 effector memory subpopulation.

Ongoing longitudinal prospective study in MS patients undergoing DMF treatment. A panel of T and B lymphocyte subpopulations in peripheral blood is analyzed by flow cytometry. Patients with a complete follow-up of more than 1 year are classified as: NEDA, MEDA (minimal clinical or radiological activity) or EDA.

To date, 48 patients have been analyzed. After a 2.66 (1-5) years follow-up, we find 39.6% in NEDA, 25% in MEDA, and 16.7% in EDA.

The changes induced on the subpopulations (increase T [CD4 and CD8] and B naïve, and decrease T central memory (CM) and effector memory (EfM), and B memory) remain stable in the long term (> 2 years), being most prominent in NEDA patients. In these, lower percentages of Th1 CM and EfM pre-treatment (p = 0.009, p = 0.002), as well as of Th1, Th17 and Th1-like Th17 CM (p <0.001, p = 0.002, p = 0.012) and Th1 and Th17 EfM (p <0.001, p = 0.034) during the first 12 months of treatment are found. MEDA patients appear to behave like EDA patients in changes in Th1/Th17/Th1-like Th17.

The changes induced by DMF on the lymphocyte subpopulations remain stable over time. NEDA patients have an immunophenotype that seems to identify them. Immunomonitoring detects the true biological effect of the treatments.