Gene expression profiling of the effect of high-dose intravenous ig in patients with Kawasaki disease
Gene expression profiling of the effect of high-dose intravenous ig in patients with Kawasaki disease
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DOI：
10.4049/jimmunol.174.9.5837
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Terai, M
中科院分区：
文献类型：
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作者：
Abe, J;Jibiki, T;Terai, M
川崎病（Kawasaki disease， KD）是婴幼儿的一种急性血管炎，主要影响冠状动脉。静脉输注大剂量Ig （IVIG）可有效减轻全身炎症，预防KD患者冠状动脉病变。为了研究IVIG治疗效果的机制，我们检测了急性患者在IVIG治疗前后PBMC和纯化单核细胞的基因表达谱。结果表明，IVIG通过改变KD患者基因的各个功能方面来抑制活化的单核细胞和巨噬细胞。在PBMC和纯化单核细胞中常见的18个转录本中，我们选择了FCGR1A、FCGR3A、CCR2、ADM、S100A9和S100A12 6个基因，通过实时RT-PCR验证芯片结果。此外，IVIG后单核细胞Fc γ RI和Fc γ RIII的表达减少。与发热对照组相比，急性KD患者血浆中S100A8/A9异复合体水平升高，但S100A9水平未升高。此外，S100A8/A9在IVIG治疗下迅速下调。在后来发生冠状动脉瘤的患者中，发现IVIG后S100A8/A9持续升高。这些结果表明，IVIG在KD中的作用可能是通过抑制单核细胞中的一系列免疫激活基因来介导的，包括激活Fc γ Rs和S100A8/A9异复合体的基因。
Kawasaki disease (KD) is an acute vasculitis of infants and young children, preferentially affecting the coronary arteries. Intravenous infusion of high dose Ig (IVIG) effectively reduces systemic inflammation and prevents coronary artery lesions in KD. To investigate the mechanisms underlying the therapeutic effects of IVIG, we examined gene expression profiles of PBMC and purified monocytes obtained from acute patients before and after IVIG therapy. The results suggest that IVIG suppresses activated monocytes and macrophages by altering various functional aspects of the genes of KD patients. Among the 18 commonly decreased transcripts in both PBMC and purified monocytes, we selected six genes, FCGR1A, FCGR3A, CCR2, ADM, S100A9, and S100A12, and confirmed the microarray results by real-time RT-PCR. Moreover, the expressions of Fc gamma RI and Fc gamma RIII on monocytes were reduced after IVIG. Plasma S100A8/A9 heterocomplex, but not S100A9, levels were elevated in patients with acute KD compared with those in febrile controls. Furthermore, S100A8/A9 was rapidly down-regulated in response to IVIG therapy. Persistent elevation of S100A8/A9 after IVIG was found in patients who later developed coronary aneurysms. These results indicate that the effects of IVIG in KD may be mediated by suppression of an array of immune activation genes in monocytes, including those activating Fc gamma Rs and the S100A8/A9 heterocomplex.