Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Actividades para captar y vacunar a la población susceptible en la Comunidad Valenciana

Eliminating measles and rubella and preventing congenital rubella infection plan of WHO highlighted the need to assess vaccination coverage and develop strategies to improve it and eliminate pockets of low immunization coverage. It exists evidence about the potential role of immunization information systems to improve coverage. The aim of this article is to describe the actions taken from the Vaccine Information System of Valencian Community addressed to improve the vaccination coverage. The Vaccine Information System is a comprehensive information system that allows the management of vaccination programs. It is connected to other systems so that decisions related to vaccinations as clinical and epidemiological management is facilitated. Regarding the role in improving vaccination coverage, the Vaccine Information System facilitates the implementation of all alternatives that have been proven effective: calculate coverage and feedback of results, active recruitment, cooperate with the epidemiological surveillance and logistics management of vaccines. We can conclude, therefore, that the Vaccine Information System is a useful tool to improve vaccination coverage and thus contribute to the elimination of measles and rubella.La Organización Mundial de la Salud en su revisión del Plan de eliminación del sarampión y la rubéola remarcó la necesidad de evaluar las coberturas vacunales y desarrollar estrategias para mejorarlas y eliminar las bolsas de baja cobertura vacunal. Existe evidencia del papel que pueden jugar los sistemas de información vacunal para mejorar estas coberturas. El objetivo del presente artículo es describir las acciones realizadas a partir del Sistema de Información Vacunal de la Comunidad Valenciana en la mejora de las coberturas vacunales. Se trata de un sistema integral que permite le gestión de los programas de vacunación. Está conectado con otros sistemas de manera que se facilita la toma de decisiones relacionadas con las vacunaciones, tanto clínicas como epidemiológicas o de gestión. Respecto al papel que juega en la mejora de las coberturas vacunales, el Sistema de Información Vacunal facilita la realización de todas las alternativas que se han demostrado efectivas: cálculo de coberturas y difusión de resultados, actividades de captación activa, colaboración con los servicios de vigilancia epidemiológica, gestión de la logística de las vacunas. Se puede concluir, por tanto, que el Sistema de Información Vacunal es una herramienta útil para mejorar las coberturas vacunales y contribuir así a la eliminación del sarampión y la rubéola

Prescripción de vacunas no incluidas en el calendario vacunal en la Comunitat Valenciana durante el período 2004-2009

Background: In the context of the policies of rational use of medicine, and in order to achieve an efficient management of the vaccinations programs, we expect to know the number of packings and cost of prescribed vaccines not included in the vaccination programs of Valencian Community and its departments during 2009 and to analyze its evolution since 2004, focusing on an analysis of Heptavalent pneumococcal conjugate vaccine in children under two years old. Methods: Retrospective descriptive study to analyze the prescriptions of vaccines in Valencian Community during 2009 and its evolution since 2004. Variables: vaccine availability, number of packings, group of beneficiary (actives/pensioners), department, and cost of prescriptions. Data sources: Gestor de Prestación Farmacéutica (GAIA) and Sistema Información Poblacional (SIP). Results: In 2009 prescribed vaccines on official national health system prescription forms that are not included in vaccination programs, supposed a cost of 683.445,71 € corresponding to 17.353 packings (87% of the total prescribed vaccines). Heptavalent pneumococcal conjugate vaccine generated 72% of the total cost of vaccines not included in the vaccination programs. The trend from 2004 to 2009 shows an increase in expenditure of 735.334 € (24,66%) in 2005 from which there takes place a marked and gradual decrease that reaches 1.562.650,67 € (-228.64%). The cost by departments of prescriptions per 1000 children under two years old of pneumococcal conjugate vaccine ranges between 17.377 and 324 €. Conclusions: The declining trend of prescriptions, mainly of pneumococcal conjugate vaccines, continues during 2009. A great interdepartmental variability is observed, nevertheless, in rates of prescription that should be corrected.Fundamentos: En el marco de las políticas de uso racional del medicamento, y al objeto de conseguir una gestión eficiente de los programas de vacunaciones, el objetivo de este trabajo es conocer el número de envases de las vacunas prescritas no incluidas en los programas de vacunación en la Comunitat Valenciana y en sus departamentos de salud, así como el gasto que produjeron en 2009, y analizar la evolución desde 2004, centrando el análisis en la vacuna heptavalente conjugada frente al Streptococcus pneumoniae en menores de dos años. Método: Estudio descriptivo retrospectivo de las vacunas prescritas mediante receta en la Comunitat Valenciana durante el año 2009 y su evolución desde 2004. Variables: número de envases, tipo de beneficiario (activo/pensionista), departamento y gasto generado. Fuentes: Gestor de Prestación Farmacéutica (GAIA) y Sistema Información Poblacional (SIP). Resultados: En 2009 la prescripción mediante receta de vacunas no incluidas en los programas de vacunación generó un gasto de 683.445,71 € correspondiente a 17.353 envases, lo que supuso el 87% del total del gasto en vacunas recetadas. La vacuna frente al S. pneumoniae generó el 72% del gasto total de las vacunas no incluidas en el calendario. La evolución 2004-2009 muestra un aumento del gasto de 735.334 € (24,66%) en 2005 a partir del cual se produjo un descenso acusado y paulatino que alcanzó los 1.562.650,67 € (-228.64%). El gasto por departamentos para la vacuna del neumococo conjugada heptavalente por mil niños/as menores de dos años osciló entre 17.377 y 324 €. Conclusiones: La tendencia descendente del gasto en recetas prescritas se mantuvo durante 2009, fundamentalmente de vacunas conjugadas frente a neumococo. No obstante, se observó gran variabilidad interdepartamental en las tasas de prescripción que debe ser corregida