Contributions
Abstract: P433
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Introduction: Multiple sclerosis (MS) is an autoimmune disease of the CNS characterized by a multifocal inflammatory immune response mediated by lymphocytes and macrophages. Its pathogenesis is conditioned by the interaction of multiple genetic and environmental factors.Recent reports highlight the role of microRNAs in the control of various immunological processes, including the development and maturation of T and B lymphocytes, the presentation of antigens, and cytokine production. In this context, the differential expression of some miRNAs, and their role in various autoimmune diseases, including MS, have been investigated. The role of microRNA-146a (miRNA-146a) as a negative regulator of immune activation is well established. This molecule is involved in a negative feedback loop: it is induced by NF-kB, but also inhibits its activation.
Objectives: To evaluate the expression of circulating miRNA-146a in the serum of Portuguese MS patients.
Methods: The study included 76 MS patients (Mean age: 45±12 years; 59.2% female; Mean disease duration: 13±8 years; 59 Relapse Remitting MS; 17 Progressive MS) and 78 matched healthy controls (HC) (Mean age: 44±10 years; 60.3% female). RNA extraction from serum was performed using the miRNeasy Serum/Plasma Kit. Relative expression values were calculated using the 2-ΔΔCt method. Differences in ΔCt were evaluated using a two-tailed Student's t-test.
Results: Significantly increased expression of miRNA-146a was found in the serum of MS patients compared with HC (fold change 5.86; p< 0.0001). The RRMS group had higher serum levels of miRNA-146a compared with the Progressive MS group (26.8 vs. 25.4, p=0.036).
Conclusions: Circulating miRNAs have emerged as potential biomarkers for several human diseases including MS. One of the miRNAs that seems to be differentially regulated in MS, in different tissues and cells, is miR-146a: it has been found to be increased in brain lesions, serum and blood-derived immune cells. In this study we also found higher serum levels of miRNA-146a in MS patients. Relapse remitting patients presented the highest values, which agrees with the notion that inflammatory mechanisms are predominant in this stage of the disease.
These are preliminary results of a country-wide multicentric project that will study several immunologically relevant microRNAs in a large cohort of MS patients.
This work was supported by BIEM.
Disclosure: Andreia Bettencourt: nothing to disclose; Bárbara Leal: nothing to disclose; Raquel Samões: nothing to disclose; Ana Paula Sousa: nothing to disclose; Ernestina Santos: nothing to disclose; Ana Aires: nothing to disclose; Joana Guimarães: nothing to disclose; Maria José Sá: nothing to disclose; FJ Ros Forteza: nothing to disclose; Inês Correia: nothing to disclose; Lívia Sousa: nothing to disclose; João Ferreia: nothing to disclose; João Sá: nothing to disclose; Paulo Pinho e Costa: nothing to disclose; Berta Martins da Silva: nothing to disclose; Ana Martins da Silva: nothing to disclose.
Abstract: P433
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Introduction: Multiple sclerosis (MS) is an autoimmune disease of the CNS characterized by a multifocal inflammatory immune response mediated by lymphocytes and macrophages. Its pathogenesis is conditioned by the interaction of multiple genetic and environmental factors.Recent reports highlight the role of microRNAs in the control of various immunological processes, including the development and maturation of T and B lymphocytes, the presentation of antigens, and cytokine production. In this context, the differential expression of some miRNAs, and their role in various autoimmune diseases, including MS, have been investigated. The role of microRNA-146a (miRNA-146a) as a negative regulator of immune activation is well established. This molecule is involved in a negative feedback loop: it is induced by NF-kB, but also inhibits its activation.
Objectives: To evaluate the expression of circulating miRNA-146a in the serum of Portuguese MS patients.
Methods: The study included 76 MS patients (Mean age: 45±12 years; 59.2% female; Mean disease duration: 13±8 years; 59 Relapse Remitting MS; 17 Progressive MS) and 78 matched healthy controls (HC) (Mean age: 44±10 years; 60.3% female). RNA extraction from serum was performed using the miRNeasy Serum/Plasma Kit. Relative expression values were calculated using the 2-ΔΔCt method. Differences in ΔCt were evaluated using a two-tailed Student's t-test.
Results: Significantly increased expression of miRNA-146a was found in the serum of MS patients compared with HC (fold change 5.86; p< 0.0001). The RRMS group had higher serum levels of miRNA-146a compared with the Progressive MS group (26.8 vs. 25.4, p=0.036).
Conclusions: Circulating miRNAs have emerged as potential biomarkers for several human diseases including MS. One of the miRNAs that seems to be differentially regulated in MS, in different tissues and cells, is miR-146a: it has been found to be increased in brain lesions, serum and blood-derived immune cells. In this study we also found higher serum levels of miRNA-146a in MS patients. Relapse remitting patients presented the highest values, which agrees with the notion that inflammatory mechanisms are predominant in this stage of the disease.
These are preliminary results of a country-wide multicentric project that will study several immunologically relevant microRNAs in a large cohort of MS patients.
This work was supported by BIEM.
Disclosure: Andreia Bettencourt: nothing to disclose; Bárbara Leal: nothing to disclose; Raquel Samões: nothing to disclose; Ana Paula Sousa: nothing to disclose; Ernestina Santos: nothing to disclose; Ana Aires: nothing to disclose; Joana Guimarães: nothing to disclose; Maria José Sá: nothing to disclose; FJ Ros Forteza: nothing to disclose; Inês Correia: nothing to disclose; Lívia Sousa: nothing to disclose; João Ferreia: nothing to disclose; João Sá: nothing to disclose; Paulo Pinho e Costa: nothing to disclose; Berta Martins da Silva: nothing to disclose; Ana Martins da Silva: nothing to disclose.