Serum progranulin levels are elevated in patients with systemic lupus erythematosus, reflecting disease activity.
Serum progranulin levels are elevated in patients with systemic lupus erythematosus, reflecting disease activity.
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DOI：
10.1186/ar4087
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发表时间：
2012-11-11
影响因子：
4.9
通讯作者：
Akashi K
中科院分区：
文献类型：
--
作者：
Tanaka A;Tsukamoto H;Mitoma H;Kiyohara C;Ueda N;Ayano M;Ohta S;Inoue Y;Arinobu Y;Niiro H;Horiuchi T;Akashi K
颗粒蛋白前体（PGRN）是颗粒蛋白（GRN）的前体，颗粒蛋白是由寡核苷酸（CpG）-DNA诱发的Toll样受体9（TLR 9）信号传导的可溶性辅因子。由于TLR 9信号在系统性红斑狼疮（SLE）中起着重要作用，我们研究了PGRN是否参与SLE的发病机制。采用酶联免疫吸附法（ELISA）检测68例SLE患者和60例健康对照者血清PGRN和IL-6水平。我们评估了血清PGRN水平和疾病活动指数之间的相关性。在疾病通过治疗得到改善后，重新评估来自初始评估时具有高PGRN滴度（>80 ng/ml）的患者的血清。我们还测量了与（a）在存在或不存在重组人PGRN（rhPGRN）的情况下的寡核苷酸（CpG-B）和（B）在存在或不存在中和抗PGRN抗体的情况下的狼疮血清孵育的外周血单核细胞（PBMC）分泌的IL-6浓度。SLE患者血清PGRN水平显著高于健康对照组。它们的水平与临床症状的活动性显著相关。它们还与临床参数值显著相关，包括SLE疾病活动指数和抗双链DNA抗体滴度，与CH 50、C3和C4水平呈负相关。此外，成功治疗系统性红斑狼疮后，血清PGRN水平显着下降。rhPGRN显着上调CpG-B刺激的PBMCs产生IL-6。患者的血清刺激PBMC产生IL-6，其被PGRN的中和显著削弱。血清PGRN水平与血清IL-6水平显著相关。血清PGRN可作为SLE疾病活动性的一个有用的生物标志物。PGRN可能通过增强TLR 9信号通路参与SLE的发病。
Progranulin (PGRN) is the precursor of granulin (GRN), a soluble cofactor for toll-like receptor 9 (TLR9) signaling evoked by oligonucleotide (CpG)-DNA. Because TLR9 signaling plays an important role in systemic lupus erythematosus (SLE), we investigated whether PGRN is involved in the pathogenesis of SLE. We measured concentrations of serum PGRN and interleukin-6 (IL-6) with enzyme-linked immunosorbent assay (ELISA) in patients with SLE (n = 68) and in healthy controls (n = 60). We assessed the correlation between the serum PGRN levels and established disease-activity indexes. The sera from the patients with high PGRN titers (>80 ng/ml) at the initial evaluation were reevaluated after the disease was ameliorated by treatment. We also measured the IL-6 concentration secreted by peripheral blood mononuclear cells (PBMCs) incubated with (a) oligonucleotide (CpG-B) in the presence or absence of recombinant human PGRN (rhPGRN); and (b) lupus sera in the presence or absence of a neutralizing anti-PGRN antibody. Serum PGRN levels were significantly higher in SLE patients than healthy controls. Their levels were significantly associated with activity of clinical symptoms. They also significantly correlated with values of clinical parameters, including the SLE Disease Activity Index and anti-double-stranded DNA antibody titers, and inversely with CH50, C3, and C4 levels. Moreover, serum PGRN levels significantly decreased after successful treatment of SLE. The rhPGRN significantly upregulated the production of IL-6 by PBMCs stimulated with CpG-B. Patients' sera stimulated production of IL-6 from PBMCs, which was significantly impaired by neutralization of PGRN. The serum PGRN levels significantly correlated with the serum IL-6 levels. Serum PGRN could be a useful biomarker for disease activity of SLE. PGRN may be involved in the pathogenesis of SLE partly by enhancing the TLR9 signaling.
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影响因子：
4
作者：
Bateman, Andrew;Bennett, Hugh P. J.
通讯作者：
Bennett, Hugh P. J.
影响因子：
82.9
作者：
He, ZH;Ong, CHP;Bateman, A
通讯作者：
Bateman, A
影响因子：
15.9
作者：
Kessenbrock, Kai;Froehlich, Leopold;Jenne, Dieter E.
通讯作者：
Jenne, Dieter E.
影响因子：
9.1
作者：
Chun, Hye-Young;Chung, Jae-Wook;Suh, Chang-Hee
通讯作者：
Suh, Chang-Hee
Toll样受体9控制鼠狼疮中的抗DNA自身抗体产生。
DOI：
10.1084/jem.20050338
发表时间：
2005-07-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Christensen SR;Kashgarian M;Alexopoulou L;Flavell RA;Akira S;Shlomchik MJ
通讯作者：
Shlomchik MJ