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RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares.
Orange, Dana E; Yao, Vicky; Sawicka, Kirsty; Fak, John; Frank, Mayu O; Parveen, Salina; Blachere, Nathalie E; Hale, Caryn; Zhang, Fan; Raychaudhuri, Soumya; Troyanskaya, Olga G; Darnell, Robert B.
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  • Orange DE; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Yao V; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Sawicka K; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Fak J; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Frank MO; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Parveen S; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Blachere NE; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Hale C; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Zhang F; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Raychaudhuri S; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Troyanskaya OG; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
  • Darnell RB; From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y
N Engl J Med ; 383(3): 218-228, 2020 07 16.
Article en En | MEDLINE | ID: mdl-32668112
BACKGROUND: Rheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown. METHODS: We established a clinical and technical protocol for repeated home collection of blood in patients with rheumatoid arthritis to allow for longitudinal RNA sequencing (RNA-seq). Specimens were obtained from 364 time points during eight flares over a period of 4 years in our index patient, as well as from 235 time points during flares in three additional patients. We identified transcripts that were differentially expressed before flares and compared these with data from synovial single-cell RNA-seq. Flow cytometry and sorted-blood-cell RNA-seq in additional patients were used to validate the findings. RESULTS: Consistent changes were observed in blood transcriptional profiles 1 to 2 weeks before a rheumatoid arthritis flare. B-cell activation was followed by expansion of circulating CD45-CD31-PDPN+ preinflammatory mesenchymal, or PRIME, cells in the blood from patients with rheumatoid arthritis; these cells shared features of inflammatory synovial fibroblasts. Levels of circulating PRIME cells decreased during flares in all 4 patients, and flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells in 19 additional patients with rheumatoid arthritis. CONCLUSIONS: Longitudinal genomic analysis of rheumatoid arthritis flares revealed PRIME cells in the blood during the period before a flare and suggested a model in which these cells become activated by B cells in the weeks before a flare and subsequently migrate out of the blood into the synovium. (Funded by the National Institutes of Health and others.).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Linfocitos B / Expresión Génica / Análisis de Secuencia de ARN / Células Madre Mesenquimatosas Tipo de estudio: Diagnostic_studies / Guideline / Prognostic_studies / Risk_factors_studies Aspecto: Patient_preference Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: N Engl J Med Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Linfocitos B / Expresión Génica / Análisis de Secuencia de ARN / Células Madre Mesenquimatosas Tipo de estudio: Diagnostic_studies / Guideline / Prognostic_studies / Risk_factors_studies Aspecto: Patient_preference Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: N Engl J Med Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos