B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels.

B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels.
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DOI:
10.1186/ar1855
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发表时间:
2006
影响因子:
4.9
通讯作者:
Stohl W
Stohl W
中科院分区:
医学2区
文献类型:
--
作者:
Collins CE;Gavin AL;Migone TS;Hilbert DM;Nemazee D;Stohl W

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相当多的证据表明,B淋巴细胞刺激因子(BLyS)在小鼠和人类系统性红斑狼疮(SLE)中过度表达。然而,BLyS蛋白循环水平与人类SLE疾病活动性之间的相关性最多是适度的。这可能是由于前者不足以忠实地反映内源性BLyS过量生产,因为稳态蛋白质水平不仅受生产率的影响,还受外周利用率和排泄率的影响。BLyS mRNA水平的增加可能更好地反映了体内BLyS产生的增加,因此它们可能比BLyS蛋白的循环水平更好地与BLyS过表达的生物学和临床后遗症相关。因此,我们评估了SLE患者外周血白细胞BLyS mRNA亚型(全长BLyS和ΔBLyS)水平和血浆BLyS蛋白水平,并将这些水平与实验室和临床特征相关联。SLE患者(n = 60)的BLyS蛋白、全长BLyS mRNA和ΔBLyS mRNA水平高于类风湿关节炎患者(n = 60)或正常对照个体(n = 30)。虽然在SLE队列中全长BLyS和ΔBLyS mRNA水平与BLyS蛋白水平显著相关,但BLyS mRNA水平与血清免疫球蛋白水平和SLE疾病活动指数评分的相关性比BLyS蛋白水平更密切。此外,SLE疾病活动指数评分的变化与BLyS mRNA水平的变化比与BLyS蛋白水平的变化更密切相关,其中37例SLE患者获得了重复血液样本。因此,全长BLyS和ΔBLyS mRNA水平在SLE中升高,并且比BLyS蛋白水平与疾病活动性更密切相关。BLyS mRNA水平可能是SLE患者临床监测的一个有用的生物标志物。
Considerable evidence points to a role for B lymphocyte stimulator (BLyS) overproduction in murine and human systemic lupus erythematosus (SLE). Nevertheless, the correlation between circulating levels of BLyS protein and disease activity in human SLE is modest at best. This may be due to an inadequacy of the former to reflect endogenous BLyS overproduction faithfully, in that steady-state protein levels are affected not just by production rates but also by rates of peripheral utilization and excretion. Increased levels of BLyS mRNA may better reflect increased in vivo BLyS production, and therefore they may correlate better with biologic and clinical sequelae of BLyS overexpression than do circulating levels of BLyS protein. Accordingly, we assessed peripheral blood leukocyte levels of BLyS mRNA isoforms (full-length BLyS and ΔBLyS) and plasma BLyS protein levels in patients with SLE, and correlated these levels with laboratory and clinical features. BLyS protein, full-length BLyS mRNA, and ΔBLyS mRNA levels were greater in SLE patients (n = 60) than in rheumatoid arthritis patients (n = 60) or normal control individuals (n = 30). Although full-length BLyS and ΔBLyS mRNA levels correlated significantly with BLyS protein levels in the SLE cohort, BLyS mRNA levels were more closely associated with serum immunoglobulin levels and SLE Disease Activity Index scores than were BLyS protein levels. Moreover, changes in SLE Disease Activity Index scores were more closely associated with changes in BLyS mRNA levels than with changes in BLyS protein levels among the 37 SLE patients from whom repeat blood samples were obtained. Thus, full-length BLyS and ΔBLyS mRNA levels are elevated in SLE and are more closely associated with disease activity than are BLyS protein levels. BLyS mRNA levels may be a helpful biomarker in the clinical monitoring of SLE patients.
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发表时间: 2002-10-01
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