{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:39:36Z","timestamp":1773409176014,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T00:00:00Z","timestamp":1402358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Rituximab therapy alters all aspects of B\u2010cell participation in the disturbed immune response of rheumatoid arthritis patients. To determine the impact of B\u2010cell depletion on other immune compartments, we analysed levels of soluble and surface interleukin\u201015 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201015) along with the frequency of<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201015\u2010related subsets after rituximab treatment. We then studied the correlation of observed changes with clinical activity. Heparinized blood samples from 33 rheumatoid arthritis patients were collected on days 0, 30, 90 and 180 after each of three rituximab cycles. Serum cytokine levels were determined by<jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>. Interleukin\u201015 trans\u2010presentation was analysed by cytometry. Flow cytometry with monoclonal antibodies was performed to analyse circulating cell subsets. Interleukin\u201015 was detected in the serum of 25 patients before initiating the treatment. Rituximab then progressively reduced serum<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201015 (138\u00a0\u00b1\u00a021\u00a0pg\/ml at baseline, 48\u00a0\u00b1\u00a018\u00a0pg\/ml after third cycle,<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b703) along with<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017 (1197\u00a0\u00b1\u00a0203\u00a0pg\/ml at baseline, 623\u00a0\u00b1\u00a0213\u00a0pg\/ml after third cycle,<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b703) and tended to increase the frequency of circulating regulatory T cells (3\u00b71\u00a0\u00b1\u00a01\u00a0cells\/\u03bcl at baseline, 7\u00b77\u00a0\u00b1\u00a02\u00a0cells\/\u03bcl after third cycle). Rituximab also significantly decreased<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201015 trans\u2010presentation on surface monocytes of patients negative for<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201015 serum (mean fluorescence intensity: 4\u00b782\u00a0\u00b1\u00a01\u00b730 at baseline, 1\u00b742\u00a0\u00b1\u00a00\u00b769 after third cycle<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b705). Reduction of serum<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201015 was associated with decrease in<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup>\u00a0<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>45<jats:styled-content style=\"fixed-case\">RO<\/jats:styled-content><jats:sup>+<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content><jats:sup>+<\/jats:sup>ratio (1\u00b717\u00a0\u00b1\u00a00\u00b721 at baseline, 0\u00b736\u00a0\u00b1 0\u00b706 at third cycle,<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b702).<jats:styled-content style=\"fixed-case\">DAS<\/jats:styled-content>28, erythrocyte sedimentation rate and<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010reactive protein correlated significantly with<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup>\u00a0<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>45<jats:styled-content style=\"fixed-case\">RO<\/jats:styled-content><jats:sup>+<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content><jats:sup>+<\/jats:sup>ratio (<jats:italic>R<\/jats:italic>\u00a0=\u00a00\u00b7323,<jats:italic>R<\/jats:italic>\u00a0=\u00a00\u00b7357,<jats:italic>R<\/jats:italic>\u00a0=\u00a00\u00b7369 respectively,<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001). Our results suggest that sustained clinical improvement after rituximab treatment is associated with<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201015\/memory T\u2010cell\u2010related mechanisms beyond circulating B cells.<\/jats:p>","DOI":"10.1111\/imm.12212","type":"journal-article","created":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T19:21:37Z","timestamp":1384284097000},"page":"354-362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Rituximab\u2010induced interleukin\u201015 reduction associated with clinical improvement in rheumatoid arthritis"],"prefix":"10.1111","volume":"142","author":[{"given":"C\u00e9sar","family":"D\u00edaz\u2010Torn\u00e9","sequence":"first","affiliation":[{"name":"Rheumatology Unit Internal Medicine Department Hospital Sant Pau Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Angels","family":"Ortiz de Juana","sequence":"additional","affiliation":[{"name":"Immunology Department Hospital Sant Pau &amp; Institut Recerca Hospital Sant Pau IIB Sant Pau Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carme","family":"Geli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit Internal Medicine Department Hospital Sant Pau Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabet","family":"Cant\u00f3","sequence":"additional","affiliation":[{"name":"Immunology Department Hospital Sant Pau &amp; Institut Recerca Hospital Sant Pau IIB Sant Pau Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Laiz","sequence":"additional","affiliation":[{"name":"Rheumatology Unit Internal Medicine Department Hospital Sant Pau Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor","family":"Corominas","sequence":"additional","affiliation":[{"name":"Rheumatology Department Hospital Moises Broggi Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Casademont","sequence":"additional","affiliation":[{"name":"Internal Medicine Department Hospital Sant Pau Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep M.","family":"de Llobet","sequence":"additional","affiliation":[{"name":"Rheumatology Unit Internal Medicine Department Hospital Sant Pau Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e1ndido","family":"Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Immunology Department Hospital Sant Pau &amp; Institut Recerca Hospital Sant Pau IIB Sant Pau Barcelona 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