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Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease
NOE MACIAS SEGURA
JULIO ENRIQUE CASTAÑEDA DELGADO
YADIRA BASTIAN HERNANDEZ
DAVID DE SANTIAGO ALGARRA
JOSE DIONISIO CASTILLO ORTIZ
ANA LUISA ALEMAN NAVARRO
ELENA JAIME SANCHEZ
Edgar E. Lara-Ramírez
MARTIN ZAPATA ZUÑIGA
Leonor Enciso Moreno
Roberto González-Amaro
Cesar Ramos-Remus
José Antonio Enciso Moreno
Acceso Abierto
Atribución-NoComercial-SinDerivadas
https://doi.org/10.1371/journal.pone.0194205
"Background Little is known regarding the mechanisms underlying the loss of tolerance in the early and preclinical stages of autoimmune diseases. The aim of this work was to identify the transcriptional profile and signaling pathways associated to non-treated early rheumatoid arthritis (RA) and subjects at high risk. Several biomarker candidates for early RA are proposed. Methods Whole blood total RNA was obtained from non-treated early RA patients with < 1 year of evolution as well as from healthy first-degree relatives of patients with RA (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels against cyclic citrullinated peptides. Complementary RNA (cRNA) was synthetized and hybridized to high-density microarrays. Data was analyzed in Genespring Software and functional categories were assigned to a specific transcriptome identified in subjects with RA and FDR ACCP positive. Specific signaling pathways for genes associated to RA were identified. Gene expression was evaluated by qPCR. Receiver operating characteristic (ROC) analysis was used to evaluate these genes as biomarkers. Results A characteristic transcriptome of 551 induced genes and 4,402 repressed genes were identified in early RA patients. Bioinformatics analysis of the data identified a specific transcriptome in RA patients. Moreover, some overlapped transcriptional profiles between patients with RA and ACCP+ were identified, suggesting an up-regulated distinctive transcriptome from the preclinical stages up to progression to an early RA state. A total of 203 pathways have up-regulated genes that are shared between RA and ACCP+. Some of these genes show potential to be used as progression biomarkers for early RA with area under the curve of ROC > 0.92. These genes come from several functional categories associated to inflammation, Wnt signaling and type I interferon pathways. Conclusion The presence of a specific transcriptome in whole blood of RA patients suggests the activation of a specific inflammatory transcriptional signature in early RA development. The set of overexpressed genes in early RA patients that are shared with ACCP+ subjects but not with ACCP- subjects, can represent a transcriptional signature involved with the transition of a preclinical to a clinical RA stage."
Public Library of Science
2018
Artículo
Macías-Segura N, Castañeda-Delgado JE, Bastian Y, Santiago-Algarra D, Castillo-Ortiz JD, Alemán-Navarro AL, et al. (2018) Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease. PLoS ONE 13(3): e0194205. https://doi.org/10.1371/journal.pone.0194205
CIENCIAS TECNOLÓGICAS
Versión publicada
publishedVersion - Versión publicada
Aparece en las colecciones: Publicaciones Científicas Biología Molecular

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