Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis

The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology an...
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Autor*in:	Cañete, Juan D [verfasserIn] Celis, Raquel Yeremenko, Nataliya Sanmartí, Raimon van Duivenvoorde, Leonie Ramírez, Julio Blijdorp, Iris García-Herrero, Carmen M Pablos, José L Baeten, Dominique L

Format:	Artikel
Sprache:	Englisch

Erschienen:	2015

Rechteinformationen:	Nutzungsrecht: © Cañete et al. 2015

Übergeordnetes Werk:	Enthalten in: Arthritis research & therapy - London : BioMed Central, 2003, 17(2015), 1, Seite 173
Übergeordnetes Werk:	volume:17 ; year:2015 ; number:1 ; pages:173

Links:	Volltext Link aufrufen Link aufrufen

DOI / URN:	10.1186/s13075-015-0688-0

Katalog-ID:	OLC1961017342

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520			\|a The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A.
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700	1		\|a García-Herrero, Carmen M \|4 oth
700	1		\|a Pablos, José L \|4 oth
700	1		\|a Baeten, Dominique L \|4 oth
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allfields	10.1186/s13075-015-0688-0 doi PQ20160617 (DE-627)OLC1961017342 (DE-599)GBVOLC1961017342 (PRQ)p1621-a11dee3eeb7daccd8e0177331b7dd23ffb85afe5f88db287c32672dc2c1c6a123 (KEY)0427448220150000017000100173ectopiclymphoidneogenesisisstronglyassociatedwitha DE-627 ger DE-627 rakwb eng 610 DNB Cañete, Juan D verfasserin aut Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A. Nutzungsrecht: © Cañete et al. 2015 Celis, Raquel oth Yeremenko, Nataliya oth Sanmartí, Raimon oth van Duivenvoorde, Leonie oth Ramírez, Julio oth Blijdorp, Iris oth García-Herrero, Carmen M oth Pablos, José L oth Baeten, Dominique L oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 17(2015), 1, Seite 173 (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:17 year:2015 number:1 pages:173 http://dx.doi.org/10.1186/s13075-015-0688-0 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26156866 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4496927&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 17 2015 1 173
spelling	10.1186/s13075-015-0688-0 doi PQ20160617 (DE-627)OLC1961017342 (DE-599)GBVOLC1961017342 (PRQ)p1621-a11dee3eeb7daccd8e0177331b7dd23ffb85afe5f88db287c32672dc2c1c6a123 (KEY)0427448220150000017000100173ectopiclymphoidneogenesisisstronglyassociatedwitha DE-627 ger DE-627 rakwb eng 610 DNB Cañete, Juan D verfasserin aut Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A. Nutzungsrecht: © Cañete et al. 2015 Celis, Raquel oth Yeremenko, Nataliya oth Sanmartí, Raimon oth van Duivenvoorde, Leonie oth Ramírez, Julio oth Blijdorp, Iris oth García-Herrero, Carmen M oth Pablos, José L oth Baeten, Dominique L oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 17(2015), 1, Seite 173 (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:17 year:2015 number:1 pages:173 http://dx.doi.org/10.1186/s13075-015-0688-0 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26156866 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4496927&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 17 2015 1 173
allfields_unstemmed	10.1186/s13075-015-0688-0 doi PQ20160617 (DE-627)OLC1961017342 (DE-599)GBVOLC1961017342 (PRQ)p1621-a11dee3eeb7daccd8e0177331b7dd23ffb85afe5f88db287c32672dc2c1c6a123 (KEY)0427448220150000017000100173ectopiclymphoidneogenesisisstronglyassociatedwitha DE-627 ger DE-627 rakwb eng 610 DNB Cañete, Juan D verfasserin aut Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A. Nutzungsrecht: © Cañete et al. 2015 Celis, Raquel oth Yeremenko, Nataliya oth Sanmartí, Raimon oth van Duivenvoorde, Leonie oth Ramírez, Julio oth Blijdorp, Iris oth García-Herrero, Carmen M oth Pablos, José L oth Baeten, Dominique L oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 17(2015), 1, Seite 173 (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:17 year:2015 number:1 pages:173 http://dx.doi.org/10.1186/s13075-015-0688-0 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26156866 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4496927&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 17 2015 1 173
allfieldsGer	10.1186/s13075-015-0688-0 doi PQ20160617 (DE-627)OLC1961017342 (DE-599)GBVOLC1961017342 (PRQ)p1621-a11dee3eeb7daccd8e0177331b7dd23ffb85afe5f88db287c32672dc2c1c6a123 (KEY)0427448220150000017000100173ectopiclymphoidneogenesisisstronglyassociatedwitha DE-627 ger DE-627 rakwb eng 610 DNB Cañete, Juan D verfasserin aut Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A. Nutzungsrecht: © Cañete et al. 2015 Celis, Raquel oth Yeremenko, Nataliya oth Sanmartí, Raimon oth van Duivenvoorde, Leonie oth Ramírez, Julio oth Blijdorp, Iris oth García-Herrero, Carmen M oth Pablos, José L oth Baeten, Dominique L oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 17(2015), 1, Seite 173 (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:17 year:2015 number:1 pages:173 http://dx.doi.org/10.1186/s13075-015-0688-0 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26156866 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4496927&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 17 2015 1 173
allfieldsSound	10.1186/s13075-015-0688-0 doi PQ20160617 (DE-627)OLC1961017342 (DE-599)GBVOLC1961017342 (PRQ)p1621-a11dee3eeb7daccd8e0177331b7dd23ffb85afe5f88db287c32672dc2c1c6a123 (KEY)0427448220150000017000100173ectopiclymphoidneogenesisisstronglyassociatedwitha DE-627 ger DE-627 rakwb eng 610 DNB Cañete, Juan D verfasserin aut Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A. Nutzungsrecht: © Cañete et al. 2015 Celis, Raquel oth Yeremenko, Nataliya oth Sanmartí, Raimon oth van Duivenvoorde, Leonie oth Ramírez, Julio oth Blijdorp, Iris oth García-Herrero, Carmen M oth Pablos, José L oth Baeten, Dominique L oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 17(2015), 1, Seite 173 (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:17 year:2015 number:1 pages:173 http://dx.doi.org/10.1186/s13075-015-0688-0 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26156866 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4496927&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 17 2015 1 173
language	English
source	Enthalten in Arthritis research & therapy 17(2015), 1, Seite 173 volume:17 year:2015 number:1 pages:173
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authorswithroles_txt_mv	Cañete, Juan D @@aut@@ Celis, Raquel @@oth@@ Yeremenko, Nataliya @@oth@@ Sanmartí, Raimon @@oth@@ van Duivenvoorde, Leonie @@oth@@ Ramírez, Julio @@oth@@ Blijdorp, Iris @@oth@@ García-Herrero, Carmen M @@oth@@ Pablos, José L @@oth@@ Baeten, Dominique L @@oth@@
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As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. 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author	Cañete, Juan D
spellingShingle	Cañete, Juan D ddc 610 Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis
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topic_title	610 DNB Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis
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title	Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis
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title_full	Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis
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title_sort	ectopic lymphoid neogenesis is strongly associated with activation of the il-23 pathway in rheumatoid synovitis
title_auth	Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis
abstract	The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A.
abstractGer	The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A.
abstract_unstemmed	The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A.
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title_short	Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis
url	http://dx.doi.org/10.1186/s13075-015-0688-0 http://www.ncbi.nlm.nih.gov/pubmed/26156866 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4496927&tool=pmcentrez&rendertype=abstract
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author2	Celis, Raquel Yeremenko, Nataliya Sanmartí, Raimon van Duivenvoorde, Leonie Ramírez, Julio Blijdorp, Iris García-Herrero, Carmen M Pablos, José L Baeten, Dominique L
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up_date	2024-07-03T23:32:03.146Z
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