{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:13:32Z","timestamp":1793754812509,"version":"4.6.1"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T00:00:00Z","timestamp":1540166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004628","name":"MedImmune","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004628","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>B cells impact the progression of systemic sclerosis (SSc; scleroderma) through multiple pathogenic mechanisms. CD19 inhibition in mice reduced skin thickness, collagen production, and autoantibody levels, consistent with CD19 expression on plasma cells (PCs), the source of antibody production. PC depletion could effectively reduce collagen deposition and inflammation in SSc; therefore, we investigated the effects of PC depletion on SSc disease activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A PC gene signature was evaluated in SSc skin biopsy samples in 2 phase I clinical trials. We assessed microarray data from tissue from public studies of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), dermatomyositis (DM), systemic lupus erythematosus (SLE), and atopic dermatitis, as well as blood from a phase IIb clinical trial in SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PC signature was elevated in SSc skin specimens compared to healthy donor skin (<jats:italic>P<\/jats:italic> = 2.28 \u00d7 10<jats:sup>\u22126<\/jats:sup>) and correlated with the baseline modified Rodnan skin thickness score (MRSS) (r = 0.64, <jats:italic>P<\/jats:italic> = 0.0004). Patients with a high PC signature at baseline showed greater improvement in the MRSS (mean \u00b1 SD change 35 \u00b1 16%; <jats:italic>P<\/jats:italic> = 6.30 \u00d7 10<jats:sup>\u22124<\/jats:sup>) following anti\u2010CD19 treatment with inebilizumab (MEDI\u2010551) than did patients with a low PC signature at baseline (mean \u00b1 SD change 8 \u00b1 12%; <jats:italic>P<\/jats:italic> = 0.104). The PC signature was overexpressed in tissue from patients with SLE, DM, COPD, interstitial lung disease, and IPF relative to controls (all fold change &gt;2; <jats:italic>P<\/jats:italic> &lt; 0.001). The PC signature also differed significantly between SLE patients with mild\u2010to\u2010moderate disease and those with severe disease (SLE Disease Activity Index cutoff at 10) (fold change 1.44; <jats:italic>P<\/jats:italic> = 3.90 \u00d7 10<jats:sup>\u22123<\/jats:sup>) and correlated significantly with the degree of emphysema in COPD (r = 0.53, <jats:italic>P<\/jats:italic> = 7.55 \u00d7 10<jats:sup>\u22128<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results support the notion that PCs have a role in the pathogenesis of SSc and other autoimmune or pulmonary indications. An elevated pretreatment PC signature was associated with increased benefit from MEDI\u2010551 in SSc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40656","type":"journal-article","created":{"date-parts":[[2018,6,29]],"date-time":"2018-06-29T06:20:28Z","timestamp":1530253228000},"page":"2087-2095","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Baseline Plasma Cell Gene Signature Predicts Improvement in Systemic Sclerosis Skin Scores Following Treatment With Inebilizumab (MEDI\u2010551) and Correlates With Disease Activity\u00a0in Systemic Lupus Erythematosus and Chronic Obstructive Pulmonary Disease"],"prefix":"10.1002","volume":"70","author":[{"given":"Katie","family":"Streicher","sequence":"first","affiliation":[{"name":"MedImmune Gaithersburg Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sriram","family":"Sridhar","sequence":"additional","affiliation":[{"name":"MedImmune Gaithersburg 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