2024-03-29T06:38:28Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1647142020-12-10T15:48:12Zcom_10261_3284com_10261_1col_10261_3285
Evaluation of Toll-like-receptor gene family variants as prognostic biomarkers in rheumatoid arthritis
Torices, Silvia
Alvarez-Rodríguez, Lorena
Varela, Ignacio
Muñoz, Pedro
Balsa, Alejandro
López-Hoyos, M.
Martinez-Taboada, Víctor
Fernández-Luna, J. L.
Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación (España)
Red Temática de Investigación Cooperativa en Cáncer (España)
Sociedad Española de Reumatología
Instituto de Investigación Marqués de Valdecilla
Ministerio de Economía y Competitividad (España)
Toll-like receptor
Rheumatoid arthritis
Prognosis
Gene variant
Rheumatoid 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 NFκB, 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-1β, IL-6 and TNFα, 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.
2018-05-11T07:19:35Z
2018-05-11T07:19:35Z
2017
2018-05-11T07:19:35Z
artículo
Immunology Letters 187: 35-40 (2017)
http://hdl.handle.net/10261/164714
10.1016/j.imlet.2017.04.011
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100003329
28495399
eng
Sí
closedAccess
Elsevier