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Additionally, the possible role of tumour necrosis factor (TNF) in regulating changes in specific peripheral blood memory B cell subsets in RA is still unclear.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>The frequency and distribution of B cell subsets in the peripheral blood and synovial membrane of active RA patients with long-standing disease have been analysed. Additionally, the possible role of TNF in causing disturbances in memory B cell subsets in RA patients was assessed in a clinical trial with the specific TNF-neutralising antibody, infliximab.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>RA patients, independent of disease duration, have a significantly lower frequency of peripheral blood pre-switch IgD<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> memory B cells than healthy individuals, whereas post-switch IgD<jats:sup>-<\/jats:sup>CD27<jats:sup>+<\/jats:sup> accumulate with increased disease duration. Notably, both pre-switch IgD<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> and post-switch IgD<jats:sup>-<\/jats:sup>CD27<jats:sup>+<\/jats:sup> memory B cells accumulate in the synovial membrane of RA patients. Finally, anti-TNF therapy increased the frequency of pre-switch IgD<jats:sup>+<\/jats:sup>CD27 memory B cells in the peripheral blood.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>The data suggest that decreases in peripheral blood IgD<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> pre-switch memory B cells in RA reflect their accumulation in the synovial tissue. Moreover, the significant increase in the peripheral blood pre-switch memory B cells in patients who underwent specific TNF-blockade with infliximab indicates that trafficking of memory B cells into inflamed tissue in RA patients is regulated by TNF and can be corrected by neutralising TNF.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar2718","type":"journal-article","created":{"date-parts":[[2009,6,6]],"date-time":"2009-06-06T00:50:38Z","timestamp":1244249438000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor"],"prefix":"10.1186","volume":"11","author":[{"given":"M Margarida","family":"Souto-Carneiro","sequence":"first","affiliation":[]},{"given":"Vijayabhanu","family":"Mahadevan","sequence":"additional","affiliation":[]},{"given":"Kazuki","family":"Takada","sequence":"additional","affiliation":[]},{"given":"Ruth","family":"Fritsch-Stork","sequence":"additional","affiliation":[]},{"given":"Toshihiro","family":"Nanki","sequence":"additional","affiliation":[]},{"given":"Margaret","family":"Brown","sequence":"additional","affiliation":[]},{"given":"Thomas A","family":"Fleisher","sequence":"additional","affiliation":[]},{"given":"Mildred","family":"Wilson","sequence":"additional","affiliation":[]},{"given":"Raphaela","family":"Goldbach-Mansky","sequence":"additional","affiliation":[]},{"given":"Peter E","family":"Lipsky","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2009,6,5]]},"reference":[{"key":"2558_CR1","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/ar1780","volume":"7","author":"GS Firestein","year":"2005","unstructured":"Firestein GS: Pathogenesis of rheumatoid arthritis: how early is early?. 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