{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:35:49Z","timestamp":1789756549733,"version":"4.0.1"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1308,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>The aim of this study was to determine the safety and potential efficacy of B-cell depletion with the anti-CD20 monoclonal antibody rituximab in patients with primary biliary cirrhosis (PBC) and an incomplete response to ursodeoxycholic acid (UDCA). This open-label study enrolled six patients with PBC and incomplete responses to UDCA to be treated with 2 doses of 1000 mg rituximab separated by 2 weeks and followed for 52 weeks. The primary endpoints were safety and changes in B-cell function. Two patients received only 1 dose of rituximab, one due to activation of latent varicella and the other due to a viral upper respiratory infection. Serum levels of total IgG, IgM, and IgA as well as anti-mitochondrial autoantibodies (AMAs) IgA and IgM decreased significantly from baseline by 16 weeks and returned to baseline levels by 36 weeks. Stimulation of B cells with CpG produced significantly less IgM at 52 weeks after treatment compared with B cells at baseline. In addition, transient decreases in memory B-cell and T-cell frequencies and an increase in CD25high CD4+ T cells were observed after treatment. These changes were associated with significant increases in mRNA levels of FoxP3 and transforming growth factor-\u03b2 (TGF-\u03b2) and a decrease in tumor necrosis factor-\u03b1 (TNF-\u03b1) in CD4+ T cells. Notably, serum alkaline phosphatase levels were significantly reduced up to 36 weeks following rituximab treatment.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion :<\/jats:title>\n                    <jats:p>\n                      <jats:bold>These data suggest that depletion of B cells influences the induction, maintenance, and activation of both B and T cells and provides a potential mechanism for treatment of patients with PBC with an incomplete response to UDCA. (Hepatology 2012)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.24748","type":"journal-article","created":{"date-parts":[[2011,10,17]],"date-time":"2011-10-17T11:45:39Z","timestamp":1318851939000},"page":"512-521","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":136,"title":["Biochemical and Immunologic Effects of Rituximab in Patients With Primary Biliary Cirrhosis and an Incomplete Response to Ursodeoxycholic Acid"],"prefix":"10.1097","volume":"55","author":[{"given":"Masanobu","family":"Tsuda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Moritoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe-Xiong","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weici","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsunori","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanji","family":"Wakabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Xiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Nakatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Vierling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Lindor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Gershwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Bowlus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20-20241201","doi-asserted-by":"crossref","first-page":"737745","DOI":"10.1002\/hep.22042","article-title":"The causes of primary biliary cirrhosis: convenient and inconvenient truths.","volume":"47","author":"Gershwin","year":"2008","journal-title":"Hepatology"},{"key":"R2-20-20241201","doi-asserted-by":"crossref","first-page":"12611273","DOI":"10.1056\/NEJMra043898","article-title":"Primary biliary cirrhosis.","volume":"353","author":"Kaplan","year":"2005","journal-title":"N Engl J Med"},{"key":"R3-20-20241201","doi-asserted-by":"crossref","first-page":"35253531","DOI":"10.4049\/jimmunol.138.10.3525","article-title":"Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis.","volume":"138","author":"Gershwin","year":"1987","journal-title":"J Immunol"},{"key":"R4-20-20241201","doi-asserted-by":"crossref","first-page":"13791387","DOI":"10.1016\/j.gastro.2003.07.013","article-title":"Distinct costimulation dependent and independent autoreactive Tcell clones in primary biliary cirrhosis.","volume":"125","author":"Kamihira","year":"2003","journal-title":"Gastroenterology"},{"key":"R5-20-20241201","doi-asserted-by":"crossref","first-page":"12311240","DOI":"10.1172\/JCI0214698","article-title":"Quantitative and functional analysis of PDCE2specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis.","volume":"109","author":"Kita","year":"2002","journal-title":"J Clin Invest"},{"key":"R6-20-20241201","doi-asserted-by":"crossref","first-page":"606618","DOI":"10.1053\/j.gastro.2006.05.056","article-title":"Autoreactive Tcell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory.","volume":"131","author":"Shimoda","year":"2006","journal-title":"Gastroenterology"},{"key":"R7-20-20241201","first-page":"636645","article-title":"IgM in primary biliary cirrhosis. 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