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Derailed B cell homeostasis in patients with mixed connective tissue disease
Abstract Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder, characterized by the presence of antibodies to U1-RNP protein. We aimed to determine phenotypic abnormalities of peripheral B cell subsets in MCTD. Blood samples were obtained from 46 MCTD patients, and 20 controls. U...
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Published in: | Human immunology 2013-07, Vol.74 (7), p.833-841 |
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description | Abstract Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder, characterized by the presence of antibodies to U1-RNP protein. We aimed to determine phenotypic abnormalities of peripheral B cell subsets in MCTD. Blood samples were obtained from 46 MCTD patients, and 20 controls. Using anti-CD19, anti-CD27, anti-IgD and anti-CD38 monoclonal antibodies, the following B cell subsets were identified by flow cytometry: (1) transitional B cells (CD19 + CD27-IgD + CD38high ); (2) naive B cells (CD19 + CD27-IgD + CD38low ); (3) non-switched memory B cells (CD19 + CD27 + IgD+); (4) switched memory B cells (CD19 + CD27 + IgD-); (5) double negative (DN) memory B cells (CD19 + CD27-IgD-) and (6) plasma cells (CD19 + CD27high IgD-). The proportion of transitional B cells, naive B cells and DN B lymphocytes was higher in MCTD than in controls. The DN B cells were positive for CD95 surface marker. This memory B cells population showed a close correlation with disease activity. The number of plasma cells was also increased, and there was an association between the number of plasma cells and the anti-U1RNP levels. Cyclophosphamide, methotrexate, and corticosteroid treatment decreased the number of DN and CD27high B cells. In conclusion, several abnormalities were found in the peripheral B-cell subsets in MCTD, which reinforces the role of derailed humoral autoimmune processes in the pathogenesis. |
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We aimed to determine phenotypic abnormalities of peripheral B cell subsets in MCTD. Blood samples were obtained from 46 MCTD patients, and 20 controls. Using anti-CD19, anti-CD27, anti-IgD and anti-CD38 monoclonal antibodies, the following B cell subsets were identified by flow cytometry: (1) transitional B cells (CD19 + CD27-IgD + CD38high ); (2) naive B cells (CD19 + CD27-IgD + CD38low ); (3) non-switched memory B cells (CD19 + CD27 + IgD+); (4) switched memory B cells (CD19 + CD27 + IgD-); (5) double negative (DN) memory B cells (CD19 + CD27-IgD-) and (6) plasma cells (CD19 + CD27high IgD-). The proportion of transitional B cells, naive B cells and DN B lymphocytes was higher in MCTD than in controls. The DN B cells were positive for CD95 surface marker. This memory B cells population showed a close correlation with disease activity. The number of plasma cells was also increased, and there was an association between the number of plasma cells and the anti-U1RNP levels. Cyclophosphamide, methotrexate, and corticosteroid treatment decreased the number of DN and CD27high B cells. In conclusion, several abnormalities were found in the peripheral B-cell subsets in MCTD, which reinforces the role of derailed humoral autoimmune processes in the pathogenesis.</description><identifier>ISSN: 0198-8859</identifier><identifier>EISSN: 1879-1166</identifier><identifier>DOI: 10.1016/j.humimm.2013.04.007</identifier><identifier>PMID: 23608739</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adrenal Cortex Hormones - administration & dosage ; Allergy and Immunology ; Antigens, CD - metabolism ; Autoantibodies - blood ; B-Lymphocyte Subsets - drug effects ; B-Lymphocyte Subsets - immunology ; Cells, Cultured ; Cyclophosphamide - administration & dosage ; Disease Progression ; Homeostasis - drug effects ; Humans ; Immunoglobulin Class Switching ; Immunologic Memory ; Immunophenotyping ; Methotrexate - administration & dosage ; Mixed Connective Tissue Disease - drug therapy ; Mixed Connective Tissue Disease - immunology ; Plasma Cells - drug effects ; Plasma Cells - immunology ; Ribonucleoprotein, U1 Small Nuclear - immunology</subject><ispartof>Human immunology, 2013-07, Vol.74 (7), p.833-841</ispartof><rights>American Society for Histocompatibility and Immunogenetics</rights><rights>2013 American Society for Histocompatibility and Immunogenetics</rights><rights>Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-41aca57d3c1404b6a62cd3d5a7cdf1fe27232e75928b18b6ce6361f15fb90d5d3</citedby><cites>FETCH-LOGICAL-c417t-41aca57d3c1404b6a62cd3d5a7cdf1fe27232e75928b18b6ce6361f15fb90d5d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23608739$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hajas, A</creatorcontrib><creatorcontrib>Barath, S</creatorcontrib><creatorcontrib>Szodoray, P</creatorcontrib><creatorcontrib>Nakken, B</creatorcontrib><creatorcontrib>Gogolak, P</creatorcontrib><creatorcontrib>Szekanecz, Z</creatorcontrib><creatorcontrib>Zold, E</creatorcontrib><creatorcontrib>Zeher, M</creatorcontrib><creatorcontrib>Szegedi, G</creatorcontrib><creatorcontrib>Bodolay, E</creatorcontrib><title>Derailed B cell homeostasis in patients with mixed connective tissue disease</title><title>Human immunology</title><addtitle>Hum Immunol</addtitle><description>Abstract Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder, characterized by the presence of antibodies to U1-RNP protein. We aimed to determine phenotypic abnormalities of peripheral B cell subsets in MCTD. Blood samples were obtained from 46 MCTD patients, and 20 controls. Using anti-CD19, anti-CD27, anti-IgD and anti-CD38 monoclonal antibodies, the following B cell subsets were identified by flow cytometry: (1) transitional B cells (CD19 + CD27-IgD + CD38high ); (2) naive B cells (CD19 + CD27-IgD + CD38low ); (3) non-switched memory B cells (CD19 + CD27 + IgD+); (4) switched memory B cells (CD19 + CD27 + IgD-); (5) double negative (DN) memory B cells (CD19 + CD27-IgD-) and (6) plasma cells (CD19 + CD27high IgD-). The proportion of transitional B cells, naive B cells and DN B lymphocytes was higher in MCTD than in controls. The DN B cells were positive for CD95 surface marker. This memory B cells population showed a close correlation with disease activity. The number of plasma cells was also increased, and there was an association between the number of plasma cells and the anti-U1RNP levels. Cyclophosphamide, methotrexate, and corticosteroid treatment decreased the number of DN and CD27high B cells. In conclusion, several abnormalities were found in the peripheral B-cell subsets in MCTD, which reinforces the role of derailed humoral autoimmune processes in the pathogenesis.</description><subject>Adrenal Cortex Hormones - administration & dosage</subject><subject>Allergy and Immunology</subject><subject>Antigens, CD - metabolism</subject><subject>Autoantibodies - blood</subject><subject>B-Lymphocyte Subsets - drug effects</subject><subject>B-Lymphocyte Subsets - immunology</subject><subject>Cells, Cultured</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Disease Progression</subject><subject>Homeostasis - drug effects</subject><subject>Humans</subject><subject>Immunoglobulin Class Switching</subject><subject>Immunologic Memory</subject><subject>Immunophenotyping</subject><subject>Methotrexate - administration & dosage</subject><subject>Mixed Connective Tissue Disease - drug therapy</subject><subject>Mixed Connective Tissue Disease - immunology</subject><subject>Plasma Cells - drug effects</subject><subject>Plasma Cells - immunology</subject><subject>Ribonucleoprotein, U1 Small Nuclear - immunology</subject><issn>0198-8859</issn><issn>1879-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v1DAQhi0EokvhHyDkI5cEj53YyQUJCrRIK3EAzpZjT7Re8rF4ktL-exxt4cCF01ye-Xpexl6CKEGAfnMsD-sYx7GUAlQpqlII84jtoDFtAaD1Y7YT0DZF09TtBXtGdBSZEKZ6yi6k0qIxqt2x_QdMLg4Y-HvucRj4YR5xpsVRJB4nfnJLxGkh_isuBz7Gu0z6eZrQL_EW-RKJVuQhEjrC5-xJ7wbCFw_1kn3_9PHb1U2x_3L9-erdvvAVmKWowHlXm6A8VKLqtNPSBxVqZ3zooUdppJJo6lY2HTSd9qiVhh7qvmtFqIO6ZK_Pc09p_rkiLXaMtF3vJpxXsqBqrVppWp3R6oz6NBMl7O0pxdGlewvCbh7t0Z492s2jFZXNlnLbq4cNazdi-Nv0R1wG3p4BzH_eRkyWfBblMcSU3dgwx_9t-HeAH-IUvRt-4D3ScV7TlB1asCStsF-3LLcoQeUYWwXqN3eCmyw</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Hajas, A</creator><creator>Barath, S</creator><creator>Szodoray, P</creator><creator>Nakken, B</creator><creator>Gogolak, P</creator><creator>Szekanecz, Z</creator><creator>Zold, E</creator><creator>Zeher, M</creator><creator>Szegedi, G</creator><creator>Bodolay, E</creator><general>Elsevier Inc</general><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>7X8</scope></search><sort><creationdate>20130701</creationdate><title>Derailed B cell homeostasis in patients with mixed connective tissue disease</title><author>Hajas, A ; Barath, S ; Szodoray, P ; Nakken, B ; Gogolak, P ; Szekanecz, Z ; Zold, E ; Zeher, M ; Szegedi, G ; Bodolay, E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-41aca57d3c1404b6a62cd3d5a7cdf1fe27232e75928b18b6ce6361f15fb90d5d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adrenal Cortex Hormones - administration & dosage</topic><topic>Allergy and Immunology</topic><topic>Antigens, CD - metabolism</topic><topic>Autoantibodies - blood</topic><topic>B-Lymphocyte Subsets - drug effects</topic><topic>B-Lymphocyte Subsets - immunology</topic><topic>Cells, Cultured</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Disease Progression</topic><topic>Homeostasis - drug effects</topic><topic>Humans</topic><topic>Immunoglobulin Class Switching</topic><topic>Immunologic Memory</topic><topic>Immunophenotyping</topic><topic>Methotrexate - administration & dosage</topic><topic>Mixed Connective Tissue Disease - drug therapy</topic><topic>Mixed Connective Tissue Disease - immunology</topic><topic>Plasma Cells - drug effects</topic><topic>Plasma Cells - immunology</topic><topic>Ribonucleoprotein, U1 Small Nuclear - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hajas, A</creatorcontrib><creatorcontrib>Barath, S</creatorcontrib><creatorcontrib>Szodoray, P</creatorcontrib><creatorcontrib>Nakken, B</creatorcontrib><creatorcontrib>Gogolak, P</creatorcontrib><creatorcontrib>Szekanecz, Z</creatorcontrib><creatorcontrib>Zold, E</creatorcontrib><creatorcontrib>Zeher, M</creatorcontrib><creatorcontrib>Szegedi, G</creatorcontrib><creatorcontrib>Bodolay, E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Human immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hajas, A</au><au>Barath, S</au><au>Szodoray, P</au><au>Nakken, B</au><au>Gogolak, P</au><au>Szekanecz, Z</au><au>Zold, E</au><au>Zeher, M</au><au>Szegedi, G</au><au>Bodolay, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Derailed B cell homeostasis in patients with mixed connective tissue disease</atitle><jtitle>Human immunology</jtitle><addtitle>Hum Immunol</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>74</volume><issue>7</issue><spage>833</spage><epage>841</epage><pages>833-841</pages><issn>0198-8859</issn><eissn>1879-1166</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Abstract Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder, characterized by the presence of antibodies to U1-RNP protein. We aimed to determine phenotypic abnormalities of peripheral B cell subsets in MCTD. Blood samples were obtained from 46 MCTD patients, and 20 controls. Using anti-CD19, anti-CD27, anti-IgD and anti-CD38 monoclonal antibodies, the following B cell subsets were identified by flow cytometry: (1) transitional B cells (CD19 + CD27-IgD + CD38high ); (2) naive B cells (CD19 + CD27-IgD + CD38low ); (3) non-switched memory B cells (CD19 + CD27 + IgD+); (4) switched memory B cells (CD19 + CD27 + IgD-); (5) double negative (DN) memory B cells (CD19 + CD27-IgD-) and (6) plasma cells (CD19 + CD27high IgD-). The proportion of transitional B cells, naive B cells and DN B lymphocytes was higher in MCTD than in controls. The DN B cells were positive for CD95 surface marker. This memory B cells population showed a close correlation with disease activity. The number of plasma cells was also increased, and there was an association between the number of plasma cells and the anti-U1RNP levels. Cyclophosphamide, methotrexate, and corticosteroid treatment decreased the number of DN and CD27high B cells. In conclusion, several abnormalities were found in the peripheral B-cell subsets in MCTD, which reinforces the role of derailed humoral autoimmune processes in the pathogenesis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23608739</pmid><doi>10.1016/j.humimm.2013.04.007</doi><tpages>9</tpages></addata></record> |
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subjects | Adrenal Cortex Hormones - administration & dosage Allergy and Immunology Antigens, CD - metabolism Autoantibodies - blood B-Lymphocyte Subsets - drug effects B-Lymphocyte Subsets - immunology Cells, Cultured Cyclophosphamide - administration & dosage Disease Progression Homeostasis - drug effects Humans Immunoglobulin Class Switching Immunologic Memory Immunophenotyping Methotrexate - administration & dosage Mixed Connective Tissue Disease - drug therapy Mixed Connective Tissue Disease - immunology Plasma Cells - drug effects Plasma Cells - immunology Ribonucleoprotein, U1 Small Nuclear - immunology |
title | Derailed B cell homeostasis in patients with mixed connective tissue disease |
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