Contributions
Abstract: EP1474
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: Multiple sclerosis (MS) is thought to be caused by a complex interaction between genetic and environmental factors. With the advent of new technologies, it has become increasingly clear that the cellular populations involved in immune responses are heterogeneous, and that multiple mechanisms may be involved in the pathogenesis of MS. The general picture which emerges from the studies on MS pathogenesis underlies the notion that all immune cell subpopulations are involved in disease induction and/or progression. Moreover, it is also clear that immune responses, both physiological and aberrant, are triggered by a very small number of cells within distinct cell subtypes. Thus, in order to identify unequivocally the subpopulations which are predominantly involved in the damage to myelin, a multivalent approach is required: each cell type must be classified and the pattern of expressed markers must be followed during the course of the disease, and monitored during therapy.
Methods: Serum cytokines, chemokines and growth factors and peripheral blood leukocyte (PBL) phenotypes were analyzed in patients undergoing treatment with glatiramer acetate 40 mg/gml (GA40) as part of the PhIV CONFIDENCE trial. Serum and PBLs were collected at baseline (BL) prior to GA40 treatment and at 3,6 and 12 months after initiating GA40.
Results: Compared to BL, GA40 treatment resulted in reduced pro-inflammatory cytokine production by all the analysed subsets of stimulated innate immune cells, and reduced activation by CD4 and CD8 T cells. For instance, monocytes produced less GM-CSF, a cytokine whose prominent role in neuroinflammation has recently been unveiled, and non classical monocytes reduced their release of IL6 and TNF-a.
Conclusions: In the present work we have used a strategy which has provided a comprehensive picture of markers in MS that change significantly in patients treated with DMT. The main findings indicate that over the course of 12 months after initiating GA40, there is a significant reduction in the production of proinflammatory cytokines by all the myeloid cell subsets that have been analysed. To this reduced cytokine production by innate immune cells corresponds a decrease in the activation and consequent functional response of cells of the adaptive arm of the immune response: indeed a lower frequency of activation was detected in all T cell compartments.
Disclosure: This study was supported by Teva.
Luca Battistini has received research grants from Teva, Merck Serono and Baxter and received funding for traveling and honoraria for speaking or consultation fees from Merck Serono, Teva, and Baxter.
The other authors have no disclosure to declare.
Abstract: EP1474
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: Multiple sclerosis (MS) is thought to be caused by a complex interaction between genetic and environmental factors. With the advent of new technologies, it has become increasingly clear that the cellular populations involved in immune responses are heterogeneous, and that multiple mechanisms may be involved in the pathogenesis of MS. The general picture which emerges from the studies on MS pathogenesis underlies the notion that all immune cell subpopulations are involved in disease induction and/or progression. Moreover, it is also clear that immune responses, both physiological and aberrant, are triggered by a very small number of cells within distinct cell subtypes. Thus, in order to identify unequivocally the subpopulations which are predominantly involved in the damage to myelin, a multivalent approach is required: each cell type must be classified and the pattern of expressed markers must be followed during the course of the disease, and monitored during therapy.
Methods: Serum cytokines, chemokines and growth factors and peripheral blood leukocyte (PBL) phenotypes were analyzed in patients undergoing treatment with glatiramer acetate 40 mg/gml (GA40) as part of the PhIV CONFIDENCE trial. Serum and PBLs were collected at baseline (BL) prior to GA40 treatment and at 3,6 and 12 months after initiating GA40.
Results: Compared to BL, GA40 treatment resulted in reduced pro-inflammatory cytokine production by all the analysed subsets of stimulated innate immune cells, and reduced activation by CD4 and CD8 T cells. For instance, monocytes produced less GM-CSF, a cytokine whose prominent role in neuroinflammation has recently been unveiled, and non classical monocytes reduced their release of IL6 and TNF-a.
Conclusions: In the present work we have used a strategy which has provided a comprehensive picture of markers in MS that change significantly in patients treated with DMT. The main findings indicate that over the course of 12 months after initiating GA40, there is a significant reduction in the production of proinflammatory cytokines by all the myeloid cell subsets that have been analysed. To this reduced cytokine production by innate immune cells corresponds a decrease in the activation and consequent functional response of cells of the adaptive arm of the immune response: indeed a lower frequency of activation was detected in all T cell compartments.
Disclosure: This study was supported by Teva.
Luca Battistini has received research grants from Teva, Merck Serono and Baxter and received funding for traveling and honoraria for speaking or consultation fees from Merck Serono, Teva, and Baxter.
The other authors have no disclosure to declare.