Contributions
Abstract: EP1577
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Dimethyl fumarate (DMF) is a fumaric acid ester approved for the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS). Several descriptive studies have shown that DMF affects adaptive immunity by shifting the balance between an inflammatory to a tolerogenic profile in Peripheral Blood Mononuclear Cells (PBMCs). However, little is known about DMF effects on innate immunity
Objective: To improve our understanding of DMF-induced changes in monocyte and lymphocyte subpopulations and to establish a possible association with response to treatment that could predict No Evidence of Disease Activity (NEDA) status at 2 years.
Methods: PBMCs from 10 healthy controls and 22 RRMS patients were analysed by flow cytometry at baseline and after 12 months of DMF treatment. Specific antibodies were used to identify different subsets of monocytes and lymphocytes. Clinical outcomes NEDA3 and NEDA4 were measured at 1 and 2 years of follow-up and patients were divided into two groups based on their NEDA status. The non-parametric Mann-Whitney test was used to compare clinical and cytometry data before and after 12 months of treatment as well as the differences between the two groups. The Bonferroni's correction for multiple comparisons was used considering as significant p-value < 0.0005. Correlations between cell populations and response to treatment were established using a negative binomial regression model.
Results: Mean age of our sample of patients was 41+/-9.6 years, presenting similar conditions of disability and disease activity. In accordance with previous findings, DMF treatment produced an increase in the number of naïve T cells and a significant reduction in the number of effector, central memory and IFN-gamma+ T lymphocytes, and of memory and regulatory B lymphocytes. In addition, we have newly found that DMF reduces the number of IL2+ producing T cells. After 2 years, 65% of patients were NEDA3 and only 1 patient was NEDA4. Interestingly, we have found a decrease in the number of intermediate monocytes after 1 year of DMF treatment, only present in patients who were EDA3 at 2 years (9.9%+/-3.8 at baseline versus 4.9%+/-0.9 after 1 year of DMF treatment, p< 0.0008), while NEDA3 patients were resistant to this decrease.
Conclusions: DMF exerts an immunomodulatory effect on adaptive immunity but also on innate immunity, producing differential changes in the intermediate monocyte subset than can be associated with an optimal response to treatment.
Disclosure: Antonio García Merino: has received honoraria for lecturing, consulting or travel expenses from Bayer, Biogen-Idec, Merck, Teva, Novartis, Roche, Almirall and Genzyme, and research grants from Merck and Novartis.
Irene Moreno Torres: has received honoraria for lecturing and travel expenses from Merck, Teva, Novartis, and Genzyme.
Ruth García Hernández: has received honoraria for lecturing and travel expenses from Teva, Novartis, and Genzyme.
Luis Rodríguez Esparragoza: has received honoraria for lecturing and travel expenses from Novartis.
The other authors do not have any conflicts of interest to report.
Abstract: EP1577
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Dimethyl fumarate (DMF) is a fumaric acid ester approved for the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS). Several descriptive studies have shown that DMF affects adaptive immunity by shifting the balance between an inflammatory to a tolerogenic profile in Peripheral Blood Mononuclear Cells (PBMCs). However, little is known about DMF effects on innate immunity
Objective: To improve our understanding of DMF-induced changes in monocyte and lymphocyte subpopulations and to establish a possible association with response to treatment that could predict No Evidence of Disease Activity (NEDA) status at 2 years.
Methods: PBMCs from 10 healthy controls and 22 RRMS patients were analysed by flow cytometry at baseline and after 12 months of DMF treatment. Specific antibodies were used to identify different subsets of monocytes and lymphocytes. Clinical outcomes NEDA3 and NEDA4 were measured at 1 and 2 years of follow-up and patients were divided into two groups based on their NEDA status. The non-parametric Mann-Whitney test was used to compare clinical and cytometry data before and after 12 months of treatment as well as the differences between the two groups. The Bonferroni's correction for multiple comparisons was used considering as significant p-value < 0.0005. Correlations between cell populations and response to treatment were established using a negative binomial regression model.
Results: Mean age of our sample of patients was 41+/-9.6 years, presenting similar conditions of disability and disease activity. In accordance with previous findings, DMF treatment produced an increase in the number of naïve T cells and a significant reduction in the number of effector, central memory and IFN-gamma+ T lymphocytes, and of memory and regulatory B lymphocytes. In addition, we have newly found that DMF reduces the number of IL2+ producing T cells. After 2 years, 65% of patients were NEDA3 and only 1 patient was NEDA4. Interestingly, we have found a decrease in the number of intermediate monocytes after 1 year of DMF treatment, only present in patients who were EDA3 at 2 years (9.9%+/-3.8 at baseline versus 4.9%+/-0.9 after 1 year of DMF treatment, p< 0.0008), while NEDA3 patients were resistant to this decrease.
Conclusions: DMF exerts an immunomodulatory effect on adaptive immunity but also on innate immunity, producing differential changes in the intermediate monocyte subset than can be associated with an optimal response to treatment.
Disclosure: Antonio García Merino: has received honoraria for lecturing, consulting or travel expenses from Bayer, Biogen-Idec, Merck, Teva, Novartis, Roche, Almirall and Genzyme, and research grants from Merck and Novartis.
Irene Moreno Torres: has received honoraria for lecturing and travel expenses from Merck, Teva, Novartis, and Genzyme.
Ruth García Hernández: has received honoraria for lecturing and travel expenses from Teva, Novartis, and Genzyme.
Luis Rodríguez Esparragoza: has received honoraria for lecturing and travel expenses from Novartis.
The other authors do not have any conflicts of interest to report.