{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:47:00Z","timestamp":1789001220673,"version":"build-2803163510"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1339,"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":[[2012,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>The cross\u2013talk of cluster of differentiation (CD)40\/CD40 ligand (CD40L) plays a key role in CD4+ T\u2013cell priming, B\u2013cell terminal maturation, and immunoglobulin (Ig) class\u2013switch recombination. Genetic defects in the CD40L lead to a disorder characterized by elevated concentrations of serum IgM and immunodeficiency. Patients with primary biliary cirrhosis (PBC) characteristically show circulating antimitochondrial antibodies (AMAs), liver\u2013infiltrating autoreactive T lymphocytes against mitochondrial antigens, and high levels of IgM. We hypothesized that CD40L may play a key role in the pathogenesis of the elevated serum IgM and analyzed genetic and epigenetic modifications of the gene coding for CD40L in CD4+ and CD8+ T cells isolated from circulating mononuclear cells from PBC patients and healthy controls. We herein demonstrate significantly lower levels of DNA methylation of the CD40L promoter in CD4+ T cells from PBC patients, as compared with controls, and this decreased methylation was inversely correlated with levels of serum IgM in PBC patients.<\/jats:bold>\n                      <jats:bold>Conclusion<\/jats:bold>\n                      <jats:bold>: The findings of an absence of genetic modifications of the CD40L gene, in concert with decreased DNA methylation of the CD40L promoter in PBC patients, suggests that environmental factors, rather than genetics, must play a major role in the pathogenesis of elevated serum IgM in PBC. (Hepatology 2012)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.24630","type":"journal-article","created":{"date-parts":[[2011,8,31]],"date-time":"2011-08-31T21:06:48Z","timestamp":1314824808000},"page":"153-160","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":122,"title":["Immunoglobulin M Levels Inversely Correlate With CD40 Ligand Promoter Methylation in Patients With Primary Biliary 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