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Abnormally activated B cells play a key role in the pathogenesis of SLE, but their measure in clinical practice is currently not recommended. Here, we studied peripheral B cells to identify a valid biomarker. We analyzed peripheral B cells in a discovery cohort of 30 SLE patients compared to 30 healthy controls (HC) using mass cytometry and unsupervised clustering analysis. The relevant B cell populations were subsequently studied by flow cytometry in a validation cohort of 63 SLE patients, 28 autoimmune diseases controls and 39 HC. Our data show an increased frequency of B cell populations with activated phenotype in SLE compared to healthy and autoimmune diseases controls. These cells uniformly lacked the expression of CD21 and CD27. Measurement of CD21\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    B cells in the blood identified patients with active disease and their frequency correlated with disease severity. Interestingly, we did not observe an increase in the frequency of CD21\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    B cells in patients with clinically inactive disease but with elevated conventional biomarkers (anti-dsDNA and complement levels). Accordingly, measurement of CD21\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    B cells represents a robust and easily accessible biomarker to assess the activity of the disease in SLE patients.\n                  <\/jats:p>","DOI":"10.1038\/s41598-022-12775-4","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T05:03:14Z","timestamp":1654146194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Measurement of circulating CD21\u2212CD27\u2212 B lymphocytes in SLE patients is associated with disease activity independently of conventional serological biomarkers"],"prefix":"10.1038","volume":"12","author":[{"given":"Alice","family":"Horisberger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Humbel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Fluder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Bellanger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Fenwick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camillo","family":"Ribi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Comte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"issue":"1","key":"12775_CR1","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1177\/0961203318817132","volume":"28","author":"K Tselios","year":"2019","unstructured":"Tselios, K. et al. Disease course patterns in systemic lupus erythematosus. Lupus 28(1), 114\u2013122 (2019).","journal-title":"Lupus"},{"key":"12775_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102615","volume":"119","author":"A Thanou","year":"2021","unstructured":"Thanou, A., Jupe, E., Purushothaman, M., Niewold, T. B. & Munroe, M. E. Clinical disease activity and flare in SLE: Current concepts and novel biomarkers. J. Autoimmun. 119, 102615 (2021).","journal-title":"J. Autoimmun."},{"issue":"10","key":"12775_CR3","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1093\/rheumatology\/41.10.1095","volume":"41","author":"C Gordon","year":"2002","unstructured":"Gordon, C. Long-term complications of systemic lupus erythematosus. 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