57 research outputs found

    Recomendaciones de experto sobre el bloqueo de la interleucina 6 en pacientes con artritis reumatoide

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    [Abstract] Objective: To draft recommendations on interleukin 6 (IL-6) blockade in rheumatoid arthritis (RA), based on best evidence and experience. Methods: A group of 10 experts on IL-6 blockade in RA was selected. The 2 coordinators formulated 23 questions about IL-6 blockade (indications, efficacy, safety, etc.). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Centre for Evidence Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). Results: The 8 preliminary recommendations were accepted after the Delphi process. They covered aspects such as the use of these therapies in monotherapy, in combination, in patients with refractory disease or intolerant patients, response evaluation, optimization and risk management. Conclusions: The manuscript aims to solve frequently asked questions and aid in decision making strategies when treating RA patients with IL-6 blockade.[Resumen] Objetivo. Generar recomendaciones sobre el bloqueo de la interleucina 6 (IL-6) en pacientes con artritis reumatoide (AR), basadas en la mejor evidencia y experiencia. Métodos. Se seleccionó a 10 expertos reumatólogos en el manejo de los inhibidores de la IL-6. Los 2 coordinadores generaron 23 preguntas sobre el bloqueo de la IL-6 en la AR (perfiles de indicación, eficacia, seguridad, etc.) para ser contestadas mediante una revisión sistemática de la literatura. Con base en las preguntas se definieron los criterios de inclusión y exclusión, y las estrategias de búsqueda (para interrogar Medline, Embase y la Cochrane Library). Dos revisores seleccionaron los artículos resultantes de la búsqueda. Se generaron tablas de evidencia. Paralelamente, se evaluaron abstracts de congresos de EULAR y ACR. Con toda esta evidencia los coordinadores propusieron 8 recomendaciones preliminares que se evaluaron, discutieron y votaron en una reunión de grupo nominal con el resto de los expertos. Para cada recomendación se estableció el nivel de evidencia y grado de recomendación, y el grado de acuerdo mediante un Delphi. Se definió acuerdo si al menos el 80% de los participantes contestaban sí a la recomendación (sí o no). Resultados. Las 8 recomendaciones preliminares se aceptaron tras el Delphi. Abarcan aspectos como su uso en monoterapia, en combinación, en pacientes refractarios o intolerantes, la evaluación de su respuesta, la optimización o la gestión del riesgo. Conclusiones. Este documento pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones con el bloqueo de la IL-6 en el manejo de la AR

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

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    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

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    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

    Terapias biológicas: mayor efectividad en beneficio del paciente

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    Tratamiento con rituximab de una paciente con glomerulonefritis membranoproliferativa por crioglobulinemia mixta asociada a infección por el virus de la hepatitis C

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    Comunicamos el caso de una mujer de 44 años con hepatitis crónica por virus C, que presentó microhematuria, proteinuria y deterioro progresivo de la función renal con crioglobulinemia y diagnóstico histopatológico de glomerulonefritis membranoproliferativa. Tras retirar el tratamiento con ribavirina por reacción cutánea y respuesta insuficiente a interferón se decidió el inicio de tratamiento con rituximab. Se administraron 2 ciclos de 2 dosis en 6 meses con disminución de la proteinuria y mejoría de la función renal sin observar aumento de enzimas hepáticas

    Poliartritis crónica por VIH

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    Han pasado 25 años desde que se describieron los primeros casos de SIDA en California, a raíz de 5 casos de neumonía por pneumocistis carinii en varones homosexuales1 . El VIH sigue siendo una pandemia con más de 40 millones de afectados en el mundo, aunque la mayor parte de los casos emergentes se encuentran en los países en vías de desarrollo, sobre todo África sub-sahariana, Europa del este y Asia2. La inmigración hace necesario que estemos familiarizados con las manifestaciones clínicas y manejo terapéutico de las complicaciones articulares por VIH. Presentamos el caso de una mujer procedente de África sub-sahariana que acude a urgencias por una poliartritis crónica como primera manifestación de la infección por VIH
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