Contributions
Abstract: P436
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Multiple sclerosis (MS) is an autoimmune inflammatory disease frequently associated with other autoimmune conditions such as Hashimoto"s thyroiditis (HT).
The pathogenetic mechanism underlying these associations is unknown but genetic, environmental and immune defects may have a role in the poliautoimmunity. In particular, several evidences indicated altered serum levels of vitamin D metabolites and the deregulation of regulatory T cells (Tregs) in both the diseases.
With the aim of highlighting common immune deregulated mechanisms shared by MS and HT, we investigate the levels of Tregs and the expression of important Treg differentiation genes (i.e. FoxP3, BACH2, NR4A family and PDCD5) in healthy controls (HC) and treatment-naïve patients affected by MS, HT or both the pathologies. We also evaluated the expression of the TNFAIP3 gene, a key negative regulator of inflammation involved in several autoimmune conditions and recently genetically associated to MS. Finally, we assessed the serum level of vitamin D, a key modulator of immune cell lineages including Tregs that plays a critical role in the prevention of autoimmune diseases.
We demonstrated a significant reduction of Tregs in both MS and HT patients compared to HC. Notably, the Tregs number was significantly lower in MS compared to HT, consistently with a more profound immune deregulation in this disorder. Surprisingly, the number of Tregs in patients affected by both diseases was similar to HT patients and significantly higher respect to MS patients, suggesting a "protective" role of HT against autoimmune aggression in MS. Similarly, we observed differences in gene expression between groups: the level of the anti-inflammatory and Treg differentiation genes TNFAIP3, NR4As and BACH2 were lower in MS patients, supporting a more severe immune deregulation. Conversely, HT patients displayed an over expression of the PDCD5 gene, which is important in the induction of apoptosis, a dominant phenomenon in the HT pathogenesis.
Finally, our data demonstrated very low circulating levels of 25-OH vitamin D compared to the reference values in all groups. Among these, MS patients showed the lowest levels.
In conclusion, our study suggests that MS and HT share some common pathogenetic mechanisms able to support the epidemiological observation of their frequent association, but also they present deep differences, as evidenced by the different clinical evolution and prognostic impact of the two diseases.
Disclosure:
Perga Simona: nothing di disclose
Montarolo Francesca: nothing di disclose
Martire Serena: nothing di disclose
Spadaro Michela: nothing di disclose
Giordano Ilaria: nothing di disclose
Orlandi Fabio: nothing di disclose
Bertolotto Antonio: nothing di disclose
The study was supported thanks grants from the Fondazione Italiana Sclerosi Multipla (FISM - Grant number 2010/R/7) from the Italian Ministry of Health (Bando Giovani Ricercatori 2010- Grant agreement GR-2010-2315964) and the European Community´s Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867)
Abstract: P436
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Multiple sclerosis (MS) is an autoimmune inflammatory disease frequently associated with other autoimmune conditions such as Hashimoto"s thyroiditis (HT).
The pathogenetic mechanism underlying these associations is unknown but genetic, environmental and immune defects may have a role in the poliautoimmunity. In particular, several evidences indicated altered serum levels of vitamin D metabolites and the deregulation of regulatory T cells (Tregs) in both the diseases.
With the aim of highlighting common immune deregulated mechanisms shared by MS and HT, we investigate the levels of Tregs and the expression of important Treg differentiation genes (i.e. FoxP3, BACH2, NR4A family and PDCD5) in healthy controls (HC) and treatment-naïve patients affected by MS, HT or both the pathologies. We also evaluated the expression of the TNFAIP3 gene, a key negative regulator of inflammation involved in several autoimmune conditions and recently genetically associated to MS. Finally, we assessed the serum level of vitamin D, a key modulator of immune cell lineages including Tregs that plays a critical role in the prevention of autoimmune diseases.
We demonstrated a significant reduction of Tregs in both MS and HT patients compared to HC. Notably, the Tregs number was significantly lower in MS compared to HT, consistently with a more profound immune deregulation in this disorder. Surprisingly, the number of Tregs in patients affected by both diseases was similar to HT patients and significantly higher respect to MS patients, suggesting a "protective" role of HT against autoimmune aggression in MS. Similarly, we observed differences in gene expression between groups: the level of the anti-inflammatory and Treg differentiation genes TNFAIP3, NR4As and BACH2 were lower in MS patients, supporting a more severe immune deregulation. Conversely, HT patients displayed an over expression of the PDCD5 gene, which is important in the induction of apoptosis, a dominant phenomenon in the HT pathogenesis.
Finally, our data demonstrated very low circulating levels of 25-OH vitamin D compared to the reference values in all groups. Among these, MS patients showed the lowest levels.
In conclusion, our study suggests that MS and HT share some common pathogenetic mechanisms able to support the epidemiological observation of their frequent association, but also they present deep differences, as evidenced by the different clinical evolution and prognostic impact of the two diseases.
Disclosure:
Perga Simona: nothing di disclose
Montarolo Francesca: nothing di disclose
Martire Serena: nothing di disclose
Spadaro Michela: nothing di disclose
Giordano Ilaria: nothing di disclose
Orlandi Fabio: nothing di disclose
Bertolotto Antonio: nothing di disclose
The study was supported thanks grants from the Fondazione Italiana Sclerosi Multipla (FISM - Grant number 2010/R/7) from the Italian Ministry of Health (Bando Giovani Ricercatori 2010- Grant agreement GR-2010-2315964) and the European Community´s Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867)