B Cell Tetherin: A Flow Cytometric Cell-Specific Assay for Response to Type I Interferon Predicts Clinical Features and Flares in Systemic Lupus Erythematosus.
B Cell Tetherin: A Flow Cytometric Cell-Specific Assay for Response to Type I Interferon Predicts Clinical Features and Flares in Systemic Lupus Erythematosus.
复制标题
DOI：
10.1002/art.41187
复制
发表时间：
2020-05
期刊：
影响因子：
--
通讯作者：
Vital EM
中科院分区：
文献类型：
--
作者：
El-Sherbiny YM;Md Yusof MY;Psarras A;Hensor EMA;Kabba KZ;Dutton K;Mohamed AAA;Elewaut D;McGonagle D;Tooze R;Doody G;Wittmann M;Emery P;Vital EM
I型干扰素（IFN）应答与自身免疫性疾病广泛相关，包括系统性红斑狼疮（SLE）。鉴于自身抗体在SLE中的重要作用，本研究旨在探讨B细胞特异性IFN检测结果是否与SLE活动相关。用I型IFN和II型IFN刺激B细胞和外周血单个核细胞（PBMC）。分析基因表达，并测定途径相关膜蛋白的表达。在一个发现队列（n = 156例SLE患者、30例类风湿性关节炎[RA]患者和25例健康对照）中，对一种在白细胞上广泛表达的IFN诱导蛋白质-系连蛋白（CD 317）的流式细胞术检测进行了体外验证，然后在临床上针对SLE诊断、浆母细胞扩增和不列颠群岛狼疮评估组（BILAG）2004评分进行了验证。第二，纵向验证队列的80例SLE患者也进行了评估的耀斑预测。在体外，在所有免疫细胞亚群中观察到I型IFN应答基因与细胞表面连接蛋白之间的密切细胞特异性和剂量反应关系。与II型和III型IFN相比，多个细胞亚群上的Tetherin表达选择性地响应于I型IFN的刺激。在来自发现队列的患者样本中，记忆B细胞连接蛋白显示与诊断（SLE：健康对照效应量0.11 [P = 0.003]; SLE：RA效应量0.17 [P < 0.001]）、利妥昔单抗治疗患者中的浆母细胞数量（R = 0.38，P = 0.047）和BILAG 2004最强的相关性。这些相关性与IFN评分或单核细胞连接蛋白的相关性相当或更强。在验证队列中，记忆B细胞拴系蛋白可预测未来的临床发作（风险比2.29 [95%置信区间1.01-4.64]; P = 0.022）。我们的研究结果表明，记忆B细胞表面连接蛋白，一种B细胞特异性IFN检测，与SLE诊断和疾病活动性相关，并预测耀斑比其他细胞亚群或全血检测连接蛋白，在一个独立的验证队列中确定。
Type I interferon (IFN) responses are broadly associated with autoimmune diseases, including systemic lupus erythematosus (SLE). Given the cardinal role of autoantibodies in SLE, this study was undertaken to investigate whether the findings of a B cell–specific IFN assay correlate with SLE activity. B cells and peripheral blood mononuclear cells (PBMCs) were stimulated with type I IFN and type II IFN. Gene expression was analyzed, and the expression of pathway‐related membrane proteins was determined. A flow cytometry assay for tetherin (CD317), an IFN‐induced protein ubiquitously expressed on leukocytes, was validated in vitro and then clinically against SLE diagnosis, plasmablast expansion, and the British Isles Lupus Assessment Group (BILAG) 2004 score in a discovery cohort (n = 156 SLE patients, 30 rheumatoid arthritis [RA] patients, and 25 healthy controls). A second, longitudinal validation cohort of 80 SLE patients was also evaluated for flare prediction. In vitro, a close cell‐specific and dose‐response relationship between type I IFN–responsive 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 IFN compared to types II and III IFNs. In patient samples from the discovery cohort, memory B cell tetherin showed the strongest associations with diagnosis (SLE:healthy control effect size 0.11 [P = 0.003]; SLE:RA effect size 0.17 [P < 0.001]), plasmablast numbers in rituximab‐treated patients (R = 0.38, P = 0.047), and BILAG 2004. These associations were equivalent to or stronger than those for IFN 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 1.01–4.64]; P = 0.022). Our findings indicate that memory B cell surface tetherin, a B cell–specific IFN assay, is associated with SLE 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.
登录
查看更多内容
影响因子：
7.3
作者：
Malkiel S;Barlev AN;Atisha-Fregoso Y;Suurmond J;Diamond B
通讯作者：
Diamond B
影响因子：
3.7
作者：
Kyogoku C;Smiljanovic B;Grün JR;Biesen R;Schulte-Wrede U;Häupl T;Hiepe F;Alexander T;Radbruch A;Grützkau A
通讯作者：
Grützkau A
影响因子：
13.3
作者：
Chiche, Laurent;Jourde-Chiche, Noemie;Whalen, Elizabeth;Presnell, Scott;Gersuk, Vivian;Dang, Kristen;Anguiano, Esperanza;Quinn, Charlie;Burtey, Stephane;Berland, Yvon;Kaplanski, Gilles;Harle, Jean-Robert;Pascual, Virginia;Chaussabel, Damien
通讯作者：
Chaussabel, Damien
影响因子：
4.4
作者：
Cocco, Mario;Stephenson, Sophie;Tooze, Reuben M.
通讯作者：
Tooze, Reuben M.
影响因子：
27.4
作者：
Landolt-Marticorena, C.;Bonventi, G.;Wither, J.
通讯作者：
Wither, J.