Gestores de información y comunicación científica

Filed under: reumatología — noviembre 15th, 2021 — 5:02 PM — José Pedro Martínez

Los descriptores en ciencia de la salud

El Descriptor en Ciencias de la Salud (DeCS) fue creado por la Biblioteca Regional de Medicina (BIREME): https://www.paho.org/es/bireme como un vocabulario estructurado y multilingüe para servir como un lenguaje único en la indización de artículos de revistas científicas, libros, anales de congresos, informes técnicos, y otros tipos de materiales, así como para ser usado en la búsqueda y recuperación de asuntos de la literatura científica en las fuentes de información disponibles en la Biblioteca Virtual en Salud (BVS) como LILACS, MEDLINE y otras.

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Directorio de los reumatólogos pediatras

Filed under: reumatología — enero 27th, 2021 — 12:48 PM — José Pedro Martínez

Santa Yarellis Gómez Conde santagc@infomed.sld.cu
Laydenis María del Toro Ravelo laydenis@infomed.sld.cu
Daniel Chia Proenza danielchia@infomed.sld.cu

Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease

Filed under: Artículos,Artículos científicos,reumatología,sindromes — noviembre 5th, 2020 — 10:39 PM — José Pedro Martínez

Abstract

Background

Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated in autoinflammatory disease, may define new disorders.

Methods

We analyzed peripheral-blood exome sequence data independent of clinical phenotype and inheritance pattern to identify deleterious mutations in ubiquitin-related genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, and transcriptome and cytokine profiling were performed. CRISPR-Cas9–edited zebrafish were used as an in vivo model to assess gene function.

Results

We identified 25 men with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation. (The gene UBA1 lies on the X chromosome.) In such patients, an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. Most of these 25 patients met clinical criteria for an inflammatory syndrome (relapsing polychondritis, Sweet’s syndrome, polyarteritis nodosa, or giant-cell arteritis) or a hematologic condition (myelodysplastic syndrome or multiple myeloma) or both. Mutations were found in more than half the hematopoietic stem cells, including peripheral-blood myeloid cells but not lymphocytes or fibroblasts. Mutations affecting p.Met41 resulted in loss of the canonical cytoplasmic isoform of UBA1 and in expression of a novel, catalytically impaired isoform initiated at p.Met67. Mutant peripheral-blood cells showed decreased ubiquitylation and activated innate immune pathways. Knockout of the cytoplasmic UBA1 isoform homologue in zebrafish caused systemic inflammation.

Conclusions

Using a genotype-driven approach, we identified a disorder that connects seemingly unrelated adult-onset inflammatory syndromes. We named this disorder the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. (Funded by the NIH Intramural Research Programs and the EU Horizon 2020 Research and Innovation Program.)

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