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RNA sequencing to predict response to TNF-α inhibitors reveals possible mechanism for nonresponse in smokers.
Cuppen, Bart V J; Rossato, Marzia; Fritsch-Stork, Ruth D E; Concepcion, Arno N; Linn-Rasker, Suzanne P; Bijlsma, Johannes W J; van Laar, Jacob M; Lafeber, Floris P J G; Radstake, Timothy R.
Afiliación
  • Cuppen BVJ; a Rheumatology & Clinical Immunology , University Medical Center Utrecht , Utrecht , The Netherlands.
  • Rossato M; b Laboratory of Translational Immunology , University Medical Center Utrecht , Utrecht , The Netherlands.
  • Fritsch-Stork RDE; c Department of Biotechnology , University of Verona , Verona , Italy.
  • Concepcion AN; a Rheumatology & Clinical Immunology , University Medical Center Utrecht , Utrecht , The Netherlands.
  • Linn-Rasker SP; d 1st Medical Department & Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling , Hanusch Hospital , Vienna , Austria.
  • Bijlsma JWJ; e Sigmund Freud University , Vienna , Austria.
  • van Laar JM; a Rheumatology & Clinical Immunology , University Medical Center Utrecht , Utrecht , The Netherlands.
  • Lafeber FPJG; f Rheumatology , Meander Medisch Centrum , Amersfoort , Netherlands.
  • Radstake TR; a Rheumatology & Clinical Immunology , University Medical Center Utrecht , Utrecht , The Netherlands.
Expert Rev Clin Immunol ; 14(7): 623-633, 2018 07.
Article en En | MEDLINE | ID: mdl-29808722
BACKGROUND: Several studies have employed microarray-based profiling to predict response to tumor necrosis factor-alpha inhibitors (TNFi) in rheumatoid arthritis (RA); yet efforts to validate these targets have failed to show predictive abilities acceptable for clinical practice. METHODS: The eighty most extreme responders and nonresponders to TNFi therapy were selected from the observational BiOCURA cohort. RNA sequencing was performed on mRNA from peripheral blood mononuclear cells (PBMCs) collected before initiation of treatment. The expression of pathways as well as individual gene transcripts between responders and nonresponders was investigated. Promising targets were technically replicated and validated in n = 40 new patients using qPCR assays. RESULTS: Before therapy initiation, nonresponders had lower expression of pathways related to interferon and cytokine signaling, while also showing higher levels of two genes, GPR15 and SEMA6B (p = 0.02). The two targets could be validated, however, additional analyses revealed that GPR15 and SEMA6B did not independently predict response, but were rather dose-dependent markers of smoking (p < 0.0001). CONCLUSIONS: The study did not identify new transcripts ready to use in clinical practice, yet GPR15 and SEMA6B were recognized as candidate explanatory markers for the reduced treatment success in RA smokers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Leucocitos Mononucleares / Factor de Necrosis Tumoral alfa / Antirreumáticos Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Expert Rev Clin Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Leucocitos Mononucleares / Factor de Necrosis Tumoral alfa / Antirreumáticos Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Expert Rev Clin Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido