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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Published in:Arthritis research & therapy 2015-07, Vol.17 (1), p.173-173, Article 173
Main Authors: Cañete, Juan D, Celis, Raquel, Yeremenko, Nataliya, Sanmartí, Raimon, van Duivenvoorde, Leonie, Ramírez, Julio, Blijdorp, Iris, García-Herrero, Carmen M, Pablos, José L, Baeten, Dominique L
Format: Article
Language:English
Subjects:
Aged
Analysis
Arthritis
Arthritis, Rheumatoid - pathology
B cells
Choristoma
Drug therapy
Enzyme-Linked Immunosorbent Assay
Enzymes
Female
Health aspects
Humans
Immunohistochemistry
Inflammation
Interleukin-17 - immunology
Interleukin-23 - immunology
Interleukins
Lymphoid Tissue
Male
Middle Aged
Real-Time Polymerase Chain Reaction
Rheumatoid factor
RNA
Synovial Membrane - pathology
Synovitis - immunology
Synovitis - pathology
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Celis, Raquel
Yeremenko, Nataliya
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Pablos, José L
Baeten, Dominique L
description 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 
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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 &lt; 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p &lt; 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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therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cañete, Juan D</au><au>Celis, Raquel</au><au>Yeremenko, Nataliya</au><au>Sanmartí, Raimon</au><au>van Duivenvoorde, Leonie</au><au>Ramírez, Julio</au><au>Blijdorp, Iris</au><au>García-Herrero, Carmen M</au><au>Pablos, José L</au><au>Baeten, Dominique L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis</atitle><jtitle>Arthritis research &amp; therapy</jtitle><addtitle>Arthritis Res Ther</addtitle><date>2015-07-09</date><risdate>2015</risdate><volume>17</volume><issue>1</issue><spage>173</spage><epage>173</epage><pages>173-173</pages><artnum>173</artnum><issn>1478-6354</issn><eissn>1478-6362</eissn><eissn>1478-6354</eissn><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 &lt; 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p &lt; 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><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>26156866</pmid><doi>10.1186/s13075-015-0688-0</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
Analysis
Arthritis
Arthritis, Rheumatoid - pathology
B cells
Choristoma
Drug therapy
Enzyme-Linked Immunosorbent Assay
Enzymes
Female
Health aspects
Humans
Immunohistochemistry
Inflammation
Interleukin-17 - immunology
Interleukin-23 - immunology
Interleukins
Lymphoid Tissue
Male
Middle Aged
Real-Time Polymerase Chain Reaction
Rheumatoid factor
RNA
Synovial Membrane - pathology
Synovitis - immunology
Synovitis - pathology
title Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis
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