CD84 is markedly up-regulated in Kawasaki disease arteriopathy.
CD84 is markedly up-regulated in Kawasaki disease arteriopathy.
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CD84 在川崎病动脉病中显着上调。
DOI：
10.1111/cei.12327
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发表时间：
2014
影响因子：
4.6
通讯作者：
Rowley,AH
中科院分区：
文献类型：
--
作者：
Reindel,R;Bischof,J;Kim,K-YA;Orenstein,JM;Soares,MB;Baker,SC;Shulman,ST;Perlman,EJ;Lingen,MW;Pink,AJ;Trevenen,C;Rowley,AH
川崎病（KD）治疗的主要目标是减少炎症和预防冠状动脉（CA）血栓形成，但一些儿童对目前可用的非特异性治疗没有反应。由于分子发病机制尚不清楚，新的治疗方法很难开发。为了鉴定KD CA中基因表达的异常，我们对KD CA和对照CA进行了高通量RNA测序，通过实时逆转录聚合酶链反应（RT-PCR）和免疫组织化学定位蛋白表达验证了潜在的异常基因。在急性KD型CA（发病2个月内）和慢性CA（发病5个月~ 1年）中，信号淋巴细胞活化分子CD84分别上调16倍（P< 0.01）和32倍（P< 0.01）。CD84定位于KD组织的炎症细胞。与细胞增殖、运动和存活相关的基因也在KD CA中上调，免疫激活分子MX2和SP140在慢性KD中上调。促进免疫反应和稳定血小板聚集的CD84在急慢性动脉疾病患者的KD CA中显著上调。我们提供了第一个分子证据，表明在KD严重损害的CA中，炎症反应失调持续数月至数年。
The major goals of Kawasaki disease (KD) therapy are to reduce inflammation and prevent thrombosis in the coronary arteries (CA), but some children do not respond to currently available non-specific therapies. New treatments have been difficult to develop because the molecular pathogenesis is unknown. In order to identify dysregulated gene expression in KD CA, we performed high-throughput RNA sequencing on KD and control CA, validated potentially dysregulated genes by real-time reverse transcription–polymerase chain reaction (RT–PCR) and localized protein expression by immunohistochemistry. Signalling lymphocyte activation molecule CD84 was up-regulated 16-fold (P< 0·01) in acute KD CA (within 2 months of onset) and 32-fold (P< 0·01) in chronic CA (5 months to years after onset). CD84 was localized to inflammatory cells in KD tissues. Genes associated with cellular proliferation, motility and survival were also up-regulated in KD CA, and immune activation molecules MX2 and SP140 were up-regulated in chronic KD. CD84, which facilitates immune responses and stabilizes platelet aggregates, is markedly up-regulated in KD CA in patients with acute and chronic arterial disease. We provide the first molecular evidence of dysregulated inflammatory responses persisting for months to years in CA significantly damaged by KD.