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Given the cardinal role of autoantibodies in\n SLE<\/jats:styled-content>\n , this study was undertaken to investigate whether the findings of a B cell\u2013specific\n IFN<\/jats:styled-content>\n assay correlate with\n SLE<\/jats:styled-content>\n activity.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n B cells and peripheral blood mononuclear cells (\n PBMC<\/jats:styled-content>\n s) were stimulated with type I\n IFN<\/jats:styled-content>\n and type\n II IFN<\/jats:styled-content>\n . Gene expression was analyzed, and the expression of pathway\u2010related membrane proteins was determined. A flow cytometry assay for tetherin (\n CD<\/jats:styled-content>\n 317), an\n IFN<\/jats:styled-content>\n \u2010induced protein ubiquitously expressed on leukocytes, was validated in vitro and then clinically against\n SLE<\/jats:styled-content>\n diagnosis, plasmablast expansion, and the British Isles Lupus Assessment Group (\n BILAG<\/jats:styled-content>\n ) 2004 score in a discovery cohort (n = 156\n SLE<\/jats:styled-content>\n patients, 30 rheumatoid arthritis [\n RA<\/jats:styled-content>\n ] patients, and 25 healthy controls). A second, longitudinal validation cohort of 80\n SLE<\/jats:styled-content>\n patients was also evaluated for flare prediction.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In vitro, a close cell\u2010specific and dose\u2010response relationship between type I\n IFN<\/jats:styled-content>\n \u2013responsive genes and cell surface tetherin was observed in all immune cell subsets. Tetherin expression on multiple cell subsets was selectively responsive to stimulation with type I\n IFN<\/jats:styled-content>\n compared to types\n II<\/jats:styled-content>\n and\n III IFN<\/jats:styled-content>\n s. In patient samples from the discovery cohort, memory B cell tetherin showed the strongest associations with diagnosis (\n SLE<\/jats:styled-content>\n :healthy control effect size 0.11 [\n P<\/jats:italic>\n = 0.003];\n SLE<\/jats:styled-content>\n :\n RA<\/jats:styled-content>\n effect size 0.17 [\n P<\/jats:italic>\n < 0.001]), plasmablast numbers in rituximab\u2010treated patients (R = 0.38,\n P<\/jats:italic>\n = 0.047), and\n BILAG<\/jats:styled-content>\n 2004. These associations were equivalent to or stronger than those for\n IFN<\/jats:styled-content>\n score or monocyte tetherin. Memory B cell tetherin was found to be predictive of future clinical flares in the validation cohort (hazard ratio 2.29 [95% confidence interval 1.01\u20134.64];\n P =<\/jats:italic>\n 0.022).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our findings indicate that memory B cell surface tetherin, a B cell\u2013specific\n IFN<\/jats:styled-content>\n assay, is associated with\n SLE<\/jats:styled-content>\n diagnosis and disease activity, and predicts flares better than tetherin on other cell subsets or whole blood assays, as determined in an independent validation cohort.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.41187","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T07:36:02Z","timestamp":1575531362000},"page":"769-779","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["B Cell Tetherin: A Flow Cytometric Cell\u2010Specific Assay for Response to Type I Interferon Predicts Clinical Features and Flares in Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4791-3475","authenticated-orcid":false,"given":"Yasser M.","family":"El\u2010Sherbiny","sequence":"first","affiliation":[{"name":"University of Leeds, Leeds, UK, Nottingham Trent University School of Science and Technology, Nottingham, UK, and Mansoura University Mansoura Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3131-9121","authenticated-orcid":false,"given":"Md Yuzaiful","family":"Md Yusof","sequence":"additional","affiliation":[{"name":"University of Leeds, Leeds, UK, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonios","family":"Psarras","sequence":"additional","affiliation":[{"name":"University of Leeds, Leeds, UK, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-4755","authenticated-orcid":false,"given":"Elizabeth M. A.","family":"Hensor","sequence":"additional","affiliation":[{"name":"University of Leeds, Leeds, UK, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumba Z.","family":"Kabba","sequence":"additional","affiliation":[{"name":"University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Dutton","sequence":"additional","affiliation":[{"name":"University of Leeds, Leeds, UK, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaa A. A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"University of Leeds, Leeds, UK, and Assiut University Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7468-974X","authenticated-orcid":false,"given":"Dirk","family":"Elewaut","sequence":"additional","affiliation":[{"name":"Ghent University Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"McGonagle","sequence":"additional","affiliation":[{"name":"University of Leeds, Leeds, UK, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reuben","family":"Tooze","sequence":"additional","affiliation":[{"name":"University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina","family":"Doody","sequence":"additional","affiliation":[{"name":"University of Leeds Leeds 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