Synovial B cells of rheumatoid arthritis express ZAP-70 which increases the survival and correlates with the inflammatory and autoimmune phenotype
Abstract B cells have acquired an important role in the pathogenesis of rheumatoid arthritis (RA) since B cell depletion allowed to rescue patients poorly responders to TNFα blockers. This study focused on the involvement of ZAP-70 as a bio-marker of B cells immune activation in RA. ZAP-70 expressio...
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| Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2009-04, Vol.131 (1), p.98-108 |
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| creator | Tolusso, Barbara De Santis, Maria Bosello, Silvia Gremese, Elisa Gobessi, Stefania Cuoghi, Ilaria Totaro, Michele C Bigotti, Giulio Rumi, Carlo Efremov, Dimitar G Ferraccioli, Gianfranco |
| description | Abstract B cells have acquired an important role in the pathogenesis of rheumatoid arthritis (RA) since B cell depletion allowed to rescue patients poorly responders to TNFα blockers. This study focused on the involvement of ZAP-70 as a bio-marker of B cells immune activation in RA. ZAP-70 expression in synovial fluid (SF) B cells obtained from RA patients was increased compared to SF B cells of osteoarthritis (OA) patients. Moreover we found that ZAP-70 positive/CD38 positive and ZAP-70 positive/CD5 positive B cells were enriched in SF. The analysis of B cell apoptosis in vitro showed that the percentage of ZAP-70 negative B cells spontaneously undergoing apoptosis was significantly higher than ZAP-70 positive B cells. The ZAP-70 positive B cell ratio (SF/peripheral blood (PB)) showed a positive correlation with SF autoantibody levels and with local levels of BAFF and IL6. ZAP-70 positive B cells seem to define a subset characterized by increased survival and high relationship with local inflammation and autoimmunity. |
| doi_str_mv | 10.1016/j.clim.2008.11.011 |
| format | Article |
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This study focused on the involvement of ZAP-70 as a bio-marker of B cells immune activation in RA. ZAP-70 expression in synovial fluid (SF) B cells obtained from RA patients was increased compared to SF B cells of osteoarthritis (OA) patients. Moreover we found that ZAP-70 positive/CD38 positive and ZAP-70 positive/CD5 positive B cells were enriched in SF. The analysis of B cell apoptosis in vitro showed that the percentage of ZAP-70 negative B cells spontaneously undergoing apoptosis was significantly higher than ZAP-70 positive B cells. The ZAP-70 positive B cell ratio (SF/peripheral blood (PB)) showed a positive correlation with SF autoantibody levels and with local levels of BAFF and IL6. ZAP-70 positive B cells seem to define a subset characterized by increased survival and high relationship with local inflammation and autoimmunity.</description><identifier>ISSN: 1521-6616</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1016/j.clim.2008.11.011</identifier><identifier>PMID: 19136305</identifier><identifier>CODEN: CLIIFY</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Allergy and Immunology ; Antigens, CD - biosynthesis ; Antigens, CD - immunology ; Apoptosis - immunology ; Arthritis, Rheumatoid - enzymology ; Arthritis, Rheumatoid - immunology ; Arthritis, Rheumatoid - pathology ; Autoantibodies - immunology ; B cells ; B-Cell Activating Factor - blood ; B-Cell Activating Factor - immunology ; B-Lymphocytes - enzymology ; B-Lymphocytes - immunology ; B-Lymphocytes - pathology ; BAFF ; Biological and medical sciences ; Diseases of the osteoarticular system ; Female ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene Expression ; Humans ; IL6 ; Immunohistochemistry ; Inflammatory joint diseases ; Interleukin-6 - blood ; Interleukin-6 - immunology ; Male ; Medical sciences ; Middle Aged ; Osteoarthritis - immunology ; Reverse Transcriptase Polymerase Chain Reaction ; Rheumatoid arthritis ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Synovial fluid ; Synovial Fluid - cytology ; Synovial Fluid - immunology ; ZAP-70 ; ZAP-70 Protein-Tyrosine Kinase - biosynthesis ; ZAP-70 Protein-Tyrosine Kinase - genetics ; ZAP-70 Protein-Tyrosine Kinase - immunology</subject><ispartof>Clinical immunology (Orlando, Fla.), 2009-04, Vol.131 (1), p.98-108</ispartof><rights>Elsevier Inc.</rights><rights>2008 Elsevier Inc.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-7131b3791fa8627c0c5da72cb3bd324e489a33d34a17bf7981c446915414a9cb3</citedby><cites>FETCH-LOGICAL-c470t-7131b3791fa8627c0c5da72cb3bd324e489a33d34a17bf7981c446915414a9cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clim.2008.11.011$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21378404$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19136305$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tolusso, Barbara</creatorcontrib><creatorcontrib>De Santis, Maria</creatorcontrib><creatorcontrib>Bosello, Silvia</creatorcontrib><creatorcontrib>Gremese, Elisa</creatorcontrib><creatorcontrib>Gobessi, Stefania</creatorcontrib><creatorcontrib>Cuoghi, Ilaria</creatorcontrib><creatorcontrib>Totaro, Michele C</creatorcontrib><creatorcontrib>Bigotti, Giulio</creatorcontrib><creatorcontrib>Rumi, Carlo</creatorcontrib><creatorcontrib>Efremov, Dimitar G</creatorcontrib><creatorcontrib>Ferraccioli, Gianfranco</creatorcontrib><title>Synovial B cells of rheumatoid arthritis express ZAP-70 which increases the survival and correlates with the inflammatory and autoimmune phenotype</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>Abstract B cells have acquired an important role in the pathogenesis of rheumatoid arthritis (RA) since B cell depletion allowed to rescue patients poorly responders to TNFα blockers. This study focused on the involvement of ZAP-70 as a bio-marker of B cells immune activation in RA. ZAP-70 expression in synovial fluid (SF) B cells obtained from RA patients was increased compared to SF B cells of osteoarthritis (OA) patients. Moreover we found that ZAP-70 positive/CD38 positive and ZAP-70 positive/CD5 positive B cells were enriched in SF. The analysis of B cell apoptosis in vitro showed that the percentage of ZAP-70 negative B cells spontaneously undergoing apoptosis was significantly higher than ZAP-70 positive B cells. The ZAP-70 positive B cell ratio (SF/peripheral blood (PB)) showed a positive correlation with SF autoantibody levels and with local levels of BAFF and IL6. ZAP-70 positive B cells seem to define a subset characterized by increased survival and high relationship with local inflammation and autoimmunity.</description><subject>Allergy and Immunology</subject><subject>Antigens, CD - biosynthesis</subject><subject>Antigens, CD - immunology</subject><subject>Apoptosis - immunology</subject><subject>Arthritis, Rheumatoid - enzymology</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Arthritis, Rheumatoid - pathology</subject><subject>Autoantibodies - immunology</subject><subject>B cells</subject><subject>B-Cell Activating Factor - blood</subject><subject>B-Cell Activating Factor - immunology</subject><subject>B-Lymphocytes - enzymology</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - pathology</subject><subject>BAFF</subject><subject>Biological and medical sciences</subject><subject>Diseases of the osteoarticular system</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>IL6</subject><subject>Immunohistochemistry</subject><subject>Inflammatory joint diseases</subject><subject>Interleukin-6 - blood</subject><subject>Interleukin-6 - immunology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Osteoarthritis - immunology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rheumatoid arthritis</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>Synovial fluid</subject><subject>Synovial Fluid - cytology</subject><subject>Synovial Fluid - immunology</subject><subject>ZAP-70</subject><subject>ZAP-70 Protein-Tyrosine Kinase - biosynthesis</subject><subject>ZAP-70 Protein-Tyrosine Kinase - genetics</subject><subject>ZAP-70 Protein-Tyrosine Kinase - immunology</subject><issn>1521-6616</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksGK1TAUhosozjj6Ai4kG93dmpOkTQsizAzOKAwojG7chDQ9pbm2aU3aO_Y1fGLTuUXBha4SyHf-E853kuQ50BQo5K_3qelsnzJKixQgpQAPklPIGOwk5dnD7Z7nkJ8kT0LYU0ozxvLHyQmUwHNOs9Pk5-3ihoPVHbkgBrsukKEhvsW519Nga6L91Ho72UDwx-gxBPL1_FPMJ3etNS2xznjUAQOZWiRh9gd7iFna1cQM3mOnp_h2Z6f2HrCu6XS_RvvlHtJz7NL3s0MytuiGaRnxafKo0V3AZ9t5lny5evf58v3u5uP1h8vzm50Rkk47CRwqLktodJEzaajJai2ZqXhVcyZQFKXmvOZCg6waWRZghMhLyAQIXUbsLHl1zB398H3GMKnehnUG2uEwB5VLAC5K-V-QUSGLjBURZEfQ-CEEj40ave21XxRQtSpTe7UqU6syBaCislj0Ykufqx7rPyWbowi83AAdjO4ar52x4TfHgMtCUBG5N0cO49AOFr0KxqIzWFuPZlL1YP_9j7d_lUfE2djxGy4Y9sPsXdShQAWmqLpdl2vdLVpQWoLI-C-Cqss6</recordid><startdate>20090401</startdate><enddate>20090401</enddate><creator>Tolusso, Barbara</creator><creator>De Santis, Maria</creator><creator>Bosello, Silvia</creator><creator>Gremese, Elisa</creator><creator>Gobessi, Stefania</creator><creator>Cuoghi, Ilaria</creator><creator>Totaro, Michele C</creator><creator>Bigotti, Giulio</creator><creator>Rumi, Carlo</creator><creator>Efremov, Dimitar G</creator><creator>Ferraccioli, Gianfranco</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20090401</creationdate><title>Synovial B cells of rheumatoid arthritis express ZAP-70 which increases the survival and correlates with the inflammatory and autoimmune phenotype</title><author>Tolusso, Barbara ; De Santis, Maria ; Bosello, Silvia ; Gremese, Elisa ; Gobessi, Stefania ; Cuoghi, Ilaria ; Totaro, Michele C ; Bigotti, Giulio ; Rumi, Carlo ; Efremov, Dimitar G ; Ferraccioli, Gianfranco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-7131b3791fa8627c0c5da72cb3bd324e489a33d34a17bf7981c446915414a9cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Allergy and Immunology</topic><topic>Antigens, CD - biosynthesis</topic><topic>Antigens, CD - immunology</topic><topic>Apoptosis - immunology</topic><topic>Arthritis, Rheumatoid - enzymology</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Arthritis, Rheumatoid - pathology</topic><topic>Autoantibodies - immunology</topic><topic>B cells</topic><topic>B-Cell Activating Factor - blood</topic><topic>B-Cell Activating Factor - immunology</topic><topic>B-Lymphocytes - enzymology</topic><topic>B-Lymphocytes - immunology</topic><topic>B-Lymphocytes - pathology</topic><topic>BAFF</topic><topic>Biological and medical sciences</topic><topic>Diseases of the osteoarticular system</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>IL6</topic><topic>Immunohistochemistry</topic><topic>Inflammatory joint diseases</topic><topic>Interleukin-6 - blood</topic><topic>Interleukin-6 - immunology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Osteoarthritis - immunology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Rheumatoid arthritis</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>Synovial fluid</topic><topic>Synovial Fluid - cytology</topic><topic>Synovial Fluid - immunology</topic><topic>ZAP-70</topic><topic>ZAP-70 Protein-Tyrosine Kinase - biosynthesis</topic><topic>ZAP-70 Protein-Tyrosine Kinase - genetics</topic><topic>ZAP-70 Protein-Tyrosine Kinase - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tolusso, Barbara</creatorcontrib><creatorcontrib>De Santis, Maria</creatorcontrib><creatorcontrib>Bosello, Silvia</creatorcontrib><creatorcontrib>Gremese, Elisa</creatorcontrib><creatorcontrib>Gobessi, Stefania</creatorcontrib><creatorcontrib>Cuoghi, Ilaria</creatorcontrib><creatorcontrib>Totaro, Michele C</creatorcontrib><creatorcontrib>Bigotti, Giulio</creatorcontrib><creatorcontrib>Rumi, Carlo</creatorcontrib><creatorcontrib>Efremov, Dimitar G</creatorcontrib><creatorcontrib>Ferraccioli, Gianfranco</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical immunology (Orlando, Fla.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tolusso, Barbara</au><au>De Santis, Maria</au><au>Bosello, Silvia</au><au>Gremese, Elisa</au><au>Gobessi, Stefania</au><au>Cuoghi, Ilaria</au><au>Totaro, Michele C</au><au>Bigotti, Giulio</au><au>Rumi, Carlo</au><au>Efremov, Dimitar G</au><au>Ferraccioli, Gianfranco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synovial B cells of rheumatoid arthritis express ZAP-70 which increases the survival and correlates with the inflammatory and autoimmune phenotype</atitle><jtitle>Clinical immunology (Orlando, Fla.)</jtitle><addtitle>Clin Immunol</addtitle><date>2009-04-01</date><risdate>2009</risdate><volume>131</volume><issue>1</issue><spage>98</spage><epage>108</epage><pages>98-108</pages><issn>1521-6616</issn><eissn>1521-7035</eissn><coden>CLIIFY</coden><abstract>Abstract B cells have acquired an important role in the pathogenesis of rheumatoid arthritis (RA) since B cell depletion allowed to rescue patients poorly responders to TNFα blockers. This study focused on the involvement of ZAP-70 as a bio-marker of B cells immune activation in RA. ZAP-70 expression in synovial fluid (SF) B cells obtained from RA patients was increased compared to SF B cells of osteoarthritis (OA) patients. Moreover we found that ZAP-70 positive/CD38 positive and ZAP-70 positive/CD5 positive B cells were enriched in SF. The analysis of B cell apoptosis in vitro showed that the percentage of ZAP-70 negative B cells spontaneously undergoing apoptosis was significantly higher than ZAP-70 positive B cells. The ZAP-70 positive B cell ratio (SF/peripheral blood (PB)) showed a positive correlation with SF autoantibody levels and with local levels of BAFF and IL6. ZAP-70 positive B cells seem to define a subset characterized by increased survival and high relationship with local inflammation and autoimmunity.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>19136305</pmid><doi>10.1016/j.clim.2008.11.011</doi><tpages>11</tpages></addata></record> |
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| ispartof | Clinical immunology (Orlando, Fla.), 2009-04, Vol.131 (1), p.98-108 |
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| subjects | Allergy and Immunology Antigens, CD - biosynthesis Antigens, CD - immunology Apoptosis - immunology Arthritis, Rheumatoid - enzymology Arthritis, Rheumatoid - immunology Arthritis, Rheumatoid - pathology Autoantibodies - immunology B cells B-Cell Activating Factor - blood B-Cell Activating Factor - immunology B-Lymphocytes - enzymology B-Lymphocytes - immunology B-Lymphocytes - pathology BAFF Biological and medical sciences Diseases of the osteoarticular system Female Flow Cytometry Fundamental and applied biological sciences. Psychology Fundamental immunology Gene Expression Humans IL6 Immunohistochemistry Inflammatory joint diseases Interleukin-6 - blood Interleukin-6 - immunology Male Medical sciences Middle Aged Osteoarthritis - immunology Reverse Transcriptase Polymerase Chain Reaction Rheumatoid arthritis RNA, Messenger - biosynthesis RNA, Messenger - genetics Synovial fluid Synovial Fluid - cytology Synovial Fluid - immunology ZAP-70 ZAP-70 Protein-Tyrosine Kinase - biosynthesis ZAP-70 Protein-Tyrosine Kinase - genetics ZAP-70 Protein-Tyrosine Kinase - immunology |
| title | Synovial B cells of rheumatoid arthritis express ZAP-70 which increases the survival and correlates with the inflammatory and autoimmune phenotype |
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