Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis

Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Antonio Julià [verfasserIn] Gabriela Ávila [verfasserIn] Raquel Celis [verfasserIn] Raimon Sanmartí [verfasserIn] Julio Ramírez [verfasserIn] Sara Marsal [verfasserIn] Juan D. Cañete [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Rheumatoid arthritis Anti-TNF therapy Synovial membrane Clinical response Deconvolution Peripheral T helper

Übergeordnetes Werk:	In: Arthritis Research & Therapy - BMC, 2015, 22(2020), 1, Seite 12
Übergeordnetes Werk:	volume:22 ; year:2020 ; number:1 ; pages:12

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13075-020-02287-9

Katalog-ID:	DOAJ008957185

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520			\|a Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents.
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allfields	10.1186/s13075-020-02287-9 doi (DE-627)DOAJ008957185 (DE-599)DOAJ525380ed0a63457691c9457a4b8885b8 DE-627 ger DE-627 rakwb eng RC925-935 Antonio Julià verfasserin aut Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents. Rheumatoid arthritis Anti-TNF therapy Synovial membrane Clinical response Deconvolution Peripheral T helper Diseases of the musculoskeletal system Gabriela Ávila verfasserin aut Raquel Celis verfasserin aut Raimon Sanmartí verfasserin aut Julio Ramírez verfasserin aut Sara Marsal verfasserin aut Juan D. Cañete verfasserin aut In Arthritis Research & Therapy BMC, 2015 22(2020), 1, Seite 12 (DE-627)326646418 (DE-600)2041668-4 14786362 nnns volume:22 year:2020 number:1 pages:12 https://doi.org/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/article/525380ed0a63457691c9457a4b8885b8 kostenfrei http://link.springer.com/article/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/toc/1478-6362 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2020 1 12
spelling	10.1186/s13075-020-02287-9 doi (DE-627)DOAJ008957185 (DE-599)DOAJ525380ed0a63457691c9457a4b8885b8 DE-627 ger DE-627 rakwb eng RC925-935 Antonio Julià verfasserin aut Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents. Rheumatoid arthritis Anti-TNF therapy Synovial membrane Clinical response Deconvolution Peripheral T helper Diseases of the musculoskeletal system Gabriela Ávila verfasserin aut Raquel Celis verfasserin aut Raimon Sanmartí verfasserin aut Julio Ramírez verfasserin aut Sara Marsal verfasserin aut Juan D. Cañete verfasserin aut In Arthritis Research & Therapy BMC, 2015 22(2020), 1, Seite 12 (DE-627)326646418 (DE-600)2041668-4 14786362 nnns volume:22 year:2020 number:1 pages:12 https://doi.org/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/article/525380ed0a63457691c9457a4b8885b8 kostenfrei http://link.springer.com/article/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/toc/1478-6362 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2020 1 12
allfields_unstemmed	10.1186/s13075-020-02287-9 doi (DE-627)DOAJ008957185 (DE-599)DOAJ525380ed0a63457691c9457a4b8885b8 DE-627 ger DE-627 rakwb eng RC925-935 Antonio Julià verfasserin aut Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents. Rheumatoid arthritis Anti-TNF therapy Synovial membrane Clinical response Deconvolution Peripheral T helper Diseases of the musculoskeletal system Gabriela Ávila verfasserin aut Raquel Celis verfasserin aut Raimon Sanmartí verfasserin aut Julio Ramírez verfasserin aut Sara Marsal verfasserin aut Juan D. Cañete verfasserin aut In Arthritis Research & Therapy BMC, 2015 22(2020), 1, Seite 12 (DE-627)326646418 (DE-600)2041668-4 14786362 nnns volume:22 year:2020 number:1 pages:12 https://doi.org/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/article/525380ed0a63457691c9457a4b8885b8 kostenfrei http://link.springer.com/article/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/toc/1478-6362 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2020 1 12
allfieldsGer	10.1186/s13075-020-02287-9 doi (DE-627)DOAJ008957185 (DE-599)DOAJ525380ed0a63457691c9457a4b8885b8 DE-627 ger DE-627 rakwb eng RC925-935 Antonio Julià verfasserin aut Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents. Rheumatoid arthritis Anti-TNF therapy Synovial membrane Clinical response Deconvolution Peripheral T helper Diseases of the musculoskeletal system Gabriela Ávila verfasserin aut Raquel Celis verfasserin aut Raimon Sanmartí verfasserin aut Julio Ramírez verfasserin aut Sara Marsal verfasserin aut Juan D. Cañete verfasserin aut In Arthritis Research & Therapy BMC, 2015 22(2020), 1, Seite 12 (DE-627)326646418 (DE-600)2041668-4 14786362 nnns volume:22 year:2020 number:1 pages:12 https://doi.org/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/article/525380ed0a63457691c9457a4b8885b8 kostenfrei http://link.springer.com/article/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/toc/1478-6362 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2020 1 12
allfieldsSound	10.1186/s13075-020-02287-9 doi (DE-627)DOAJ008957185 (DE-599)DOAJ525380ed0a63457691c9457a4b8885b8 DE-627 ger DE-627 rakwb eng RC925-935 Antonio Julià verfasserin aut Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents. Rheumatoid arthritis Anti-TNF therapy Synovial membrane Clinical response Deconvolution Peripheral T helper Diseases of the musculoskeletal system Gabriela Ávila verfasserin aut Raquel Celis verfasserin aut Raimon Sanmartí verfasserin aut Julio Ramírez verfasserin aut Sara Marsal verfasserin aut Juan D. Cañete verfasserin aut In Arthritis Research & Therapy BMC, 2015 22(2020), 1, Seite 12 (DE-627)326646418 (DE-600)2041668-4 14786362 nnns volume:22 year:2020 number:1 pages:12 https://doi.org/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/article/525380ed0a63457691c9457a4b8885b8 kostenfrei http://link.springer.com/article/10.1186/s13075-020-02287-9 kostenfrei https://doaj.org/toc/1478-6362 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2020 1 12
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source	In Arthritis Research & Therapy 22(2020), 1, Seite 12 volume:22 year:2020 number:1 pages:12
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authorswithroles_txt_mv	Antonio Julià @@aut@@ Gabriela Ávila @@aut@@ Raquel Celis @@aut@@ Raimon Sanmartí @@aut@@ Julio Ramírez @@aut@@ Sara Marsal @@aut@@ Juan D. Cañete @@aut@@
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The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. 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spellingShingle	Antonio Julià misc RC925-935 misc Rheumatoid arthritis misc Anti-TNF therapy misc Synovial membrane misc Clinical response misc Deconvolution misc Peripheral T helper misc Diseases of the musculoskeletal system Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis
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topic_title	RC925-935 Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis Rheumatoid arthritis Anti-TNF therapy Synovial membrane Clinical response Deconvolution Peripheral T helper
topic	misc RC925-935 misc Rheumatoid arthritis misc Anti-TNF therapy misc Synovial membrane misc Clinical response misc Deconvolution misc Peripheral T helper misc Diseases of the musculoskeletal system
topic_unstemmed	misc RC925-935 misc Rheumatoid arthritis misc Anti-TNF therapy misc Synovial membrane misc Clinical response misc Deconvolution misc Peripheral T helper misc Diseases of the musculoskeletal system
topic_browse	misc RC925-935 misc Rheumatoid arthritis misc Anti-TNF therapy misc Synovial membrane misc Clinical response misc Deconvolution misc Peripheral T helper misc Diseases of the musculoskeletal system
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title	Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis
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title_full	Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis
author_sort	Antonio Julià
journal	Arthritis Research & Therapy
journalStr	Arthritis Research & Therapy
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author_browse	Antonio Julià Gabriela Ávila Raquel Celis Raimon Sanmartí Julio Ramírez Sara Marsal Juan D. Cañete
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format_se	Elektronische Aufsätze
author-letter	Antonio Julià
doi_str_mv	10.1186/s13075-020-02287-9
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title_sort	lower peripheral helper t cell levels in the synovium are associated with a better response to anti-tnf therapy in rheumatoid arthritis
callnumber	RC925-935
title_auth	Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis
abstract	Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents.
abstractGer	Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents.
abstract_unstemmed	Abstract Background The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane. Methods Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPH association was validated using immunofluorescence. External validation was performed on an independent dataset. Results After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPH cells at baseline and a better response (P = 0.026). Lower TPH cells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r 2 = 0.58, P = 0.005) and an association with response. TPH association with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040). Conclusions A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents.
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title_short	Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis
url	https://doi.org/10.1186/s13075-020-02287-9 https://doaj.org/article/525380ed0a63457691c9457a4b8885b8 http://link.springer.com/article/10.1186/s13075-020-02287-9 https://doaj.org/toc/1478-6362
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author2	Gabriela Ávila Raquel Celis Raimon Sanmartí Julio Ramírez Sara Marsal Juan D. Cañete
author2Str	Gabriela Ávila Raquel Celis Raimon Sanmartí Julio Ramírez Sara Marsal Juan D. Cañete
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up_date	2024-07-03T21:08:44.263Z
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