Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA.
Clin Exp Immunol. 2014 Jul;177(1):203-11. doi: 10.1111/cei.12327.
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.
川崎病(KD)治疗的主要目标是减轻炎症并预防冠状动脉(CA)内的血栓形成,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,因此新的治疗方法一直难以开发。为了确定 KD CA 中失调的基因表达,我们对 KD 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)验证了潜在的失调基因,并通过免疫组织化学定位了蛋白质表达。在急性 KD CA(发病后 2 个月内)中,信号淋巴细胞激活分子 CD84 上调了 16 倍(P<0·01),在慢性 CA(发病后 5 个月至数年)中上调了 32 倍(P<0·01)。CD84 在 KD 组织中的炎症细胞中定位。KD CA 中还上调了与细胞增殖、运动和存活相关的基因,并且在慢性 KD 中,免疫激活分子 MX2 和 SP140 也上调了。CD84 促进免疫反应并稳定血小板聚集,在患有急性和慢性动脉疾病的 KD CA 中显著上调。我们提供了第一个分子证据,证明 KD 显著损伤的 CA 中炎症反应失调持续数月至数年。