ABSTRACT
BACKGROUND AND OBJECTIVES: Primary progressive multiple sclerosis (PPMS) displays a highly variable disease progression with a characteristic accumulation of disability, what makes difficult its diagnosis and efficient treatment. The identification of microRNAs (miRNAs)-based signature for the early detection in biological fluids could reveal promising biomarkers to provide new insights into defining MS clinical subtypes and potential therapeutic strategies. The objective of this cross-sectional study was to describe PPMS miRNA profiles in CSF and serum samples compared with other neurologic disease individuals (OND) and relapsing-remitting MS (RRMS). METHODS: First, a screening stage analyzing multiple miRNAs in few samples using OpenArray plates was performed. Second, individual quantitative polymerase chain reactions (qPCRs) were used to validate specific miRNAs in a greater number of samples. RESULTS: A specific profile of dysregulated circulating miRNAs (let-7b-5p and miR-143-3p) was found downregulated in PPMS CSF samples compared with OND. In addition, in serum samples, miR-20a-5p and miR-320b were dysregulated in PPMS against RRMS and OND, miR-26a-5p and miR-485-3p were downregulated in PPMS vs RRMS, and miR-142-5p was upregulated in RRMS compared with OND. DISCUSSION: We described a 2-miRNA signature in CSF of PPMS individuals and several dysregulated miRNAs in serum from patients with MS, which could be considered valuable candidates to be further studied to unravel their actual role in MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that specific miRNA profiles accurately distinguish PPMS from RRMS and other neurologic disorders.
Subject(s)
MicroRNAs , Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis , Humans , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Cross-Sectional Studies , MicroRNAs/blood , MicroRNAs/cerebrospinal fluid , MicroRNAs/genetics , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/genetics , Multiple Sclerosis, Chronic Progressive/blood , Multiple Sclerosis, Chronic Progressive/cerebrospinal fluid , Multiple Sclerosis, Chronic Progressive/genetics , RecurrenceABSTRACT
BACKGROUND: The effect of disease-modifying therapies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response is unclear. OBJECTIVES: We aim to determine the immunological responses to SARS-CoV-2 in multiple sclerosis (MS) and anti-CD20-treated patients with other autoimmune diseases (AID). METHODS: Humoral and cellular responses we determined before and 30-90 days after vaccination in patients with MS and anti-CD20-treated patients with other AID in two Catalan centers. RESULTS: 457 patients were enrolled. Findings showed that humoral response decreased under anti-CD20s or sphingosine 1-phosphate receptor modulators (S1PRM) and with longer treatment duration and increased after 4.5 months from the last anti-CD20 infusion. Cellular response decreased in S1PRM-treated. Patients on anti-CD20 can present cellular responses even in the absence of antibodies. CONCLUSION: Anti-CD20s and S1PRM modify the immunological responses to SARS-CoV-2 vaccines.
Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Multiple Sclerosis/drug therapy , SARS-CoV-2 , VaccinationABSTRACT
Contiene: 1. Consideraciones metodologicas. 2. Marco teórico. 3. Aspectos generales del comercio exterior de Bolivia. 4. Análisis del alcance, objetivos y proceso integracionistas del acuerdo de cartagena (comunidad andina), y el grado de aprovechamiento del comercio exterior de Bolivia. 5. Análisis del alcance, objetivos y mecanismos del acuerdo de complementación económica No. 36 -AAP.CE 36 (Bolivia -MERCOSUR), y el grado de aprovechamiento del comercio exterior de Bolivia. 6. Análisis del alcance, objetivos y mecanismos de los acuerdos de complementación económica No. 22 (Bolivia - Chile); No. 31 (Bolivia-México) ; No. 47 (Bolivia - Cuba), y el grado de aprovechamiento del comercio exterior de Bolivia. 7. Análisis del alcance, objetivos y mecanismos de la ley de preferencias arancelarias andinas, el sistema generalizado de preferencias; y el grado de aprovechamiento del comercio exterior de Bolivia. 8. Percepciones empresariales sobre los factores condicionantes del aprovechamiento de acuerdos comerciales por parte de Bolivia, y del proceso de negociación del área de libre comercio de las americas. 9. Conclusiones y recomendaciones.
Subject(s)
BoliviaABSTRACT
Contiene: 1. La nueva política económica el proceso de reformas estructurales y la política de integración boliviana. 2. La estructura aranceralia e impositiva del país y su relación con el comercio exterior boliviano. 3. Breve reseña de los acuerdos comerciales suscritos y/o de los que se beneficia Bolivia a nivel internacional. 4. La agenda nacional de los neuvos acuerdos comerciales. 5. Alguno resultados de las medidas de liberación económica y de la profundización de los acuerdos comerciales suscritos por Bolivia: la respuesta del empresariado privado boliviano. 6. Recomendaciones y sugerencias para favorecer el regimiento del intercambio comercial de Bolivia.
