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dc.contributor.authorTorices del Val, Silviaes_ES
dc.contributor.authorÁlvarez Rodríguez, Lorenaes_ES
dc.contributor.authorVarela Egocheaga, Ignacio es_ES
dc.contributor.authorMuñoz, Pedroes_ES
dc.contributor.authorBalsa Criado, Alejandroes_ES
dc.contributor.authorLópez Hoyos, Marcos es_ES
dc.contributor.authorMartínez Taboada, Víctor Manuel es_ES
dc.contributor.authorFernández Luna, José Luis es_ES
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.description.abstractRheumatoid arthritis (RA) is a systemic autoimmune disease whose main feature is persistent joint inflammation. Toll-like receptors (TLRs) play critical roles in the activation of innate and adaptive immune responses, and influence the activity of NF?B, a key player in chronic inflammation. We aimed at investigating the association of TLR allelic variants with susceptibility and severity of RA through a systematic, high-throughput, analysis of TLR genes. All coding exons and flanking regions of nine members of the TLR family (TLR1-9) were analyzed in 66 patients with RA and 30 healthy controls by next generation sequencing. We focussed on three single allelic variants, N248S in TLR1, Q11L in TLR7 and M1V in TLR8 based on the allelic frequencies in both patient and control populations, the predicted impact on protein function and the novelty in RA research. Analysis of these selected variants in a larger cohort of 402 patients with RA and in 208 controls revealed no association with susceptibility. However, the M1V allele was associated with a lower need for disease-modifying antirheumatic drugs (DMARDs) (p =0.008) and biologic treatments (p =0.021). Functional studies showed that the M1V variant leads to a reduced production of inflammatory cytokines, IL-1?, IL-6 and TNF?, in response to TLR8 agonists. Thus, the presence of this variant confers a significant protective effect on disease severity. These results show for the first time the association between the M1V variant of TLR8 and reduced disease severity in RA, which could have prognostic value for these patients.es_ES
dc.description.sponsorshipThis work was supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation grant PI11/02012, and grant RD12/0036/0022 from Red Temática de Investigación Cooperativa en Cáncer, Sociedad Española de Reumatología grant FER13/13 and Instituto de Investigación Valdecilla (IDIVAL) grant APG-03. I.V. is funded by programa Ramón y Cajal, Ministerio de Economia y Competitividad, Spain.es_ES
dc.format.extent6 p.es_ES
dc.rights© 2017, European Federation of Immunological Societies. Published by Elsevier B.V.Licensed under the Creative Commons Reconocimiento-NoComercial-SinObraDerivadaes_ES
dc.sourceImmunology Letters 187 (2017) 35-40es_ES
dc.subject.otherToll-like receptores_ES
dc.subject.otherRheumatoid arthritises_ES
dc.subject.otherGene variantes_ES
dc.titleEvaluation of Toll-like-receptor gene family variants as prognostic biomarkers in rheumatoid arthritises_ES

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© 2017, European Federation of Immunological Societies. Published by Elsevier B.V.Licensed under the Creative Commons Reconocimiento-NoComercial-SinObraDerivadaExcept where otherwise noted, this item's license is described as © 2017, European Federation of Immunological Societies. Published by Elsevier B.V.Licensed under the Creative Commons Reconocimiento-NoComercial-SinObraDerivada