{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:31:01Z","timestamp":1791037861625,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,30]],"date-time":"2008-12-30T00:00:00Z","timestamp":1230595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>A putative regulatory intronic polymorphism (PD1.3) in the programmed death 1 (PD\u20101) gene, a negative regulator of T cells involved in peripheral tolerance, is associated with increased risk for systemic lupus erythematosus (SLE). We undertook this study to determine the expression and function of PD\u20101 in SLE patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We genotyped 289 SLE patients and 256 matched healthy controls for PD1.3 by polymerase chain reaction\u2013restriction fragment length polymorphism analysis. Expression of PD\u20101 and its ligand, PDL\u20101, was determined in peripheral blood lymphocytes and in renal biopsy samples by flow cytometry and immunohistochemistry. A crosslinker of PD\u20101 was used to assess its effects on anti\u2010CD3\/anti\u2010CD28\u2013induced T cell proliferation and cytokine production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SLE patients had an increased frequency of the PD1.3 polymorphism (30.1%, versus 18.4% in controls; <jats:italic>P<\/jats:italic> = 0.006), with the risk A allele conferring decreased transcriptional activity in transfected Jurkat cells. Patients homozygous for PD1.3\u2014but not patients heterozygous for PD1.3\u2014had reduced basal and induced PD\u20101 expression on activated CD4+ T cells. In autologous mixed lymphocyte reactions (AMLRs), SLE patients had defective PD\u20101 induction on activated CD4+ cells; abnormalities were more pronounced among homozygotes. PD\u20101 was detected within the glomeruli and renal tubules of lupus nephritis patients, while PDL\u20101 was expressed by the renal tubules of both patients and controls. PD\u20101 crosslinking suppressed proliferation and cytokine production in both normal and lupus T cells; addition of serum from patients with active SLE significantly ameliorated this effect on proliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SLE patients display aberrant expression and function of PD\u20101 attributed to both direct and indirect effects. The expression of PD\u20101\/PDL\u20101 in renal tissue and during AMLRs suggests an important role in regulating peripheral T cell tolerance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24227","type":"journal-article","created":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T21:41:14Z","timestamp":1230759674000},"page":"207-218","source":"Crossref","is-referenced-by-count":98,"title":["Genetic, immunologic, and immunohistochemical analysis of the programmed death 1\/programmed death ligand 1 pathway in human systemic lupus erythematosus"],"prefix":"10.1002","volume":"60","author":[{"given":"George 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