TAM receptor ligands in lupus: protein S but not Gas6 levels reflect disease activity in systemic lupus erythematosus.
TAM receptor ligands in lupus: protein S but not Gas6 levels reflect disease activity in systemic lupus erythematosus.
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DOI：
10.1186/ar3088
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发表时间：
2010
影响因子：
4.9
通讯作者：
Cohen PL
中科院分区：
文献类型：
--
作者：
Suh CH;Hilliard B;Li S;Merrill JT;Cohen PL
TAM（tyro 3，axl，mer）激酶是先天免疫的关键调节剂，并且在凋亡细胞的吞噬作用中是重要的。Gas6和蛋白S是这些TAM激酶的配体，并与凋亡过程中暴露的磷脂酰丝氨酸残基结合。在动物模型中，TAM激酶的缺乏与狼疮样疾病相关。为了测试人类系统性红斑狼疮（SLE）患者是否可能具有TAM配体的缺乏水平，我们测量了SLE中的Gas 6和蛋白S水平。入选SLE患者107例。其中，45例SLE患者与正常对照组（NC）的年龄，性别和种族相匹配。Gas6和游离蛋白S用夹心酶联免疫吸附试验（ELISA）测定。总体而言，45例SLE患者和45例NC之间的Gas 6和游离蛋白S的血浆浓度没有差异。SLE患者血清游离蛋白S水平与年龄呈正相关（r = 0.2405，P = 0.0126），而Gas 6水平与年龄无相关性。个体中Gas6和游离蛋白S的浓度之间没有相关性。有浆膜炎、神经系统疾病、血液系统疾病和免疫系统疾病史的SLE患者游离蛋白S水平显著降低。Gas6水平在有神经系统疾病史的患者中升高。抗Sm或抗心磷脂IgG阳性的SLE患者血清游离蛋白S水平较低。血清游离蛋白S与补体C3（r = 0.3858，P < 0.0001）和补体C4（r = 0.4275，P < 0.0001）呈正相关。活动性BILAG血液学受累的患者，游离蛋白S水平较低，Gas6水平较高。在SLE中，具有某些类型的临床病史和疾病活动性的患者的游离蛋白S减少。游离蛋白S水平与C3和C4水平密切相关。SLE患者Gas6水平与NC患者差异不大，但在少数有神经系统疾病史的患者中升高。蛋白S水平降低与狼疮疾病活动的相关性与TAM受体在清除凋亡细胞和控制炎症中的作用一致。在这方面，蛋白S在SLE患者中的功能似乎比Gas6更重要。
The TAM (tyro 3, axl, mer) kinases are key regulators of innate immunity and are important in the phagocytosis of apoptotic cells. Gas6 and protein S are ligands for these TAM kinases and bind to phosphatidyl serine residues exposed during apoptosis. In animal models, absence of TAM kinases is associated with lupus-like disease. To test whether human systemic lupus erythematosus (SLE) patients might have deficient levels of TAM ligands, we measured Gas 6 and protein S levels in SLE. 107 SLE patients were recruited. Of these, 45 SLE patients were matched age, gender and ethnicity with normal controls (NC). Gas6 and free protein S were measured with sandwich enzyme linked immunosorbent assays (ELISAs). Overall, the plasma concentrations of Gas6 and free protein S were not different between 45 SLE patients and 45 NC. In SLE patients, the levels of free protein S were positively correlated with age (r = 0.2405, P = 0.0126), however those of Gas6 were not. There was no correlation between the concentrations of Gas6 and free protein S in individuals. Levels of free protein S were significantly lower in SLE patients with a history of serositis, neurologic disorder, hematologic disorder and immunologic disorder. Gas6 levels were elevated in patients with a history of neurologic disorder. The SLE patients with anti-Sm or anti-cardiolipin IgG showed lower free protein S levels. Circulating free protein S was positively correlated with complement component 3 (C3) (r = 0.3858, P < 0.0001) and complement component 4 (C4) (r = 0.4275, P < 0.0001). In the patients with active BILAG hematologic involvement, the levels of free protein S were lower and those of Gas6 were higher. In SLE, free protein S was decreased in patients with certain types of clinical history and disease activity. Levels of free protein S were strongly correlated with C3 and C4 levels. Gas6 levels in SLE patients differed little from levels in NC, but they were elevated in the small numbers of patients with a history of neurological disease. The correlation of decreased protein S levels with lupus disease activity is consistent with a role for the TAM receptors in scavenging apoptotic cells and controlling inflammation. Protein S appears more important functionally in SLE patients than Gas6 in this regard.
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影响因子：
20.3
作者：
Brouwer, JLR;Bijl, M;van der Meer, J
通讯作者：
van der Meer, J
影响因子：
2.3
作者：
Cohen, PL;Caricchio, R
通讯作者：
Caricchio, R
影响因子：
5.3
作者：
MANFIOLETTI, G;BRANCOLINI, C;SCHNEIDER, C
通讯作者：
SCHNEIDER, C
影响因子：
30.5
作者：
Anderson, HA;Maylock, CA;Shacter, E
通讯作者：
Shacter, E
影响因子：
--
作者：
Alciato, Federica;Sainaghi, Pier Paolo;Avanzi, Gian Carlo
通讯作者：
Avanzi, Gian Carlo