{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:28:41Z","timestamp":1773696521446,"version":"3.50.1"},"reference-count":38,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2017,4,24]]},"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>P-glycoprotein (P-gp) expression on activated lymphocytes in systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in the pathogenesis of SLE remains unclear. The aim of this study was to determine the importance of P-gp<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells in organ manifestations in refractory SLE.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The proportion of P-gp<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells was determined by flow cytometry in peripheral blood of patients with SLE (n=116) and healthy adults (n=10). Renal biopsy specimens were examined by immunohistochemistry for P-gp expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CD69 is a marker of CD4 cell activation. The proportion of both P-gp-expressing CD4<jats:sup>+<\/jats:sup> cells and CD69-expressing CD4<jats:sup>+<\/jats:sup> cells in peripheral blood was higher in SLE than control. The proportion of P-gp<jats:sup>+<\/jats:sup>CD69<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells correlated with Systemic Lupus Erythematosus Disease Activity Index and was higher in poor responders to corticosteroids. Furthermore, the proportion of P-gp<jats:sup>+<\/jats:sup>CD69<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells was significantly higher in proliferative lupus nephritis (LN) with poor response to corticosteroids. The efficacy of immunosuppressive therapy depended on the regulation of the proportion of P-gp<jats:sup>+<\/jats:sup>CD69<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells. Marked accumulation of P-gp<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells in renal interstitial tissue and high proportion of peripheral P-gp<jats:sup>+<\/jats:sup>CD69<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells were noted in patients with proliferative LN.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The results showed high proportion of P-gp<jats:sup>+<\/jats:sup>CD69<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells in peripheral blood and their accumulation in renal tissue in patients with proliferative LN refractory to CS therapy, suggesting that P-gp expression on activated CD4<jats:sup>+<\/jats:sup> T cells is a potentially useful marker for refractoriness to treatment and a novel target for treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2016-000423","type":"journal-article","created":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T20:10:27Z","timestamp":1500063027000},"page":"e000423","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Role of P-glycoprotein on CD69<sup>+<\/sup>CD4<sup>+<\/sup> cells in the pathogenesis of proliferative lupus nephritis and non-responsiveness to immunosuppressive therapy"],"prefix":"10.1136","volume":"3","author":[{"given":"Shizuyo","family":"Tsujimura","sequence":"first","affiliation":[{"name":"The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Adachi","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyoshi","family":"Saito","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2017,7,14]]},"reference":[{"key":"2025090312190396000_3.1.e000423.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2004.00803.x"},{"key":"2025090312190396000_3.1.e000423.2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21032"},{"key":"2025090312190396000_3.1.e000423.3","doi-asserted-by":"publisher","DOI":"10.1080\/03009740310004333"},{"key":"2025090312190396000_3.1.e000423.4","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.100816"},{"key":"2025090312190396000_3.1.e000423.5","first-page":"30","article-title":"Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. 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