Contributions
Abstract: P1140
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Multiple sclerosis (MS) is an inflammatory autoimmune disease, with many different immune cells involved in its pathogenesis. Keeping autoreactive cells under control is the task of specialized immune cell subsets called “regulatory” cells. The best characterized regulatory cells include regulatory T cells (Tregs), regulatory B cells (Bregs) and CD56bright NK cells.
Interferon-beta (IFN-beta) is a naturally occurring cytokine with a wide range of anti-inflammatory properties and one of the most common treatment for relapsing-remitting (RR) MS. Its mechanism of action is complex, but overall it is thought to shift cytokine production in favor of Treg-promoting cytokines, to induce IL-10 production by B cells, thus promoting the activity of Bregs, and to significantly increase the production of CD56bright NK cells.
Despite the great interest aroused by the field of regulatory cells in MS, to date an integrated analysis of Treg, Breg and CD56bright NK cells in the same subjects is still missing. To address this issue we analyzed their levels in peripheral blood of different cohorts of individuals: 25 treatment-naïve RRMS patients (T0), 9 patients treated with IFN-beta for 12 months (IFN T12), 18 treated for more than 2 years (IFN>2y) and 24 healthy controls (HC). Among patients, 9 T0 were longitudinally followed at T12.
In our study, T0 patients show a Treg down-regulation compared with HC, which is reverted by IFN-beta treatment since 12 months. On the other hand, both Breg and CD56bright NK cell levels are similar in T0 compared to HC, but are significantly increased by long-term IFN-beta treatment. In the longitudinal study, baseline levels of both Treg and Breg are not significantly different compared to T12. In particular, Tregs increase in the 55% of patients but persist stable in the others, while Bregs increase in the 33% of patients, decrease in the 55% and remain stable in the others. On the contrary, CD56bright NK cell levels at T12 are significantly higher compared to baseline, as they increase in the 88% of patients.
According to the literature and in the light of our findings, we can hypothesize that MS patients are characterized by an impairment of the regulatory compartment, which include a deficiency in the number of cells, in their function, or both. IFN-beta is able to restore this deficit, increasing the number of regulatory cells in most patients and/or promoting their activity.
Disclosure: The study was supported by Merck Serono.
The authors have nothing to disclose.
Abstract: P1140
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Multiple sclerosis (MS) is an inflammatory autoimmune disease, with many different immune cells involved in its pathogenesis. Keeping autoreactive cells under control is the task of specialized immune cell subsets called “regulatory” cells. The best characterized regulatory cells include regulatory T cells (Tregs), regulatory B cells (Bregs) and CD56bright NK cells.
Interferon-beta (IFN-beta) is a naturally occurring cytokine with a wide range of anti-inflammatory properties and one of the most common treatment for relapsing-remitting (RR) MS. Its mechanism of action is complex, but overall it is thought to shift cytokine production in favor of Treg-promoting cytokines, to induce IL-10 production by B cells, thus promoting the activity of Bregs, and to significantly increase the production of CD56bright NK cells.
Despite the great interest aroused by the field of regulatory cells in MS, to date an integrated analysis of Treg, Breg and CD56bright NK cells in the same subjects is still missing. To address this issue we analyzed their levels in peripheral blood of different cohorts of individuals: 25 treatment-naïve RRMS patients (T0), 9 patients treated with IFN-beta for 12 months (IFN T12), 18 treated for more than 2 years (IFN>2y) and 24 healthy controls (HC). Among patients, 9 T0 were longitudinally followed at T12.
In our study, T0 patients show a Treg down-regulation compared with HC, which is reverted by IFN-beta treatment since 12 months. On the other hand, both Breg and CD56bright NK cell levels are similar in T0 compared to HC, but are significantly increased by long-term IFN-beta treatment. In the longitudinal study, baseline levels of both Treg and Breg are not significantly different compared to T12. In particular, Tregs increase in the 55% of patients but persist stable in the others, while Bregs increase in the 33% of patients, decrease in the 55% and remain stable in the others. On the contrary, CD56bright NK cell levels at T12 are significantly higher compared to baseline, as they increase in the 88% of patients.
According to the literature and in the light of our findings, we can hypothesize that MS patients are characterized by an impairment of the regulatory compartment, which include a deficiency in the number of cells, in their function, or both. IFN-beta is able to restore this deficit, increasing the number of regulatory cells in most patients and/or promoting their activity.
Disclosure: The study was supported by Merck Serono.
The authors have nothing to disclose.