Nakaya Helder I, Gardner Joy, Poo Yee-Suan, Major Lee, Pulendran Bali, Suhrbier Andreas
Emory Vaccine Center at Yerkes National Primate Research Center, Atlanta, Georgia, USA.
Arthritis Rheum. 2012 Nov;64(11):3553-63. doi: 10.1002/art.34631.
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a chronic debilitating polyarthralgia/polyarthritis, for which current treatments are often inadequate. To assess whether new drugs being developed for rheumatoid arthritis (RA) might find utility in the treatment of alphaviral arthritides, we sought to determine whether the inflammatory gene expression signature of CHIKV arthritis shows any similarities with RA or collagen-induced arthritis (CIA), a mouse model of RA.
Using a recently developed animal model of CHIKV arthritis in adult wild-type mice, we generated a consensus CHIKV arthritis gene expression signature, which was used to interrogate publicly available microarray studies of RA and CIA. Pathway analyses were then performed using the overlapping gene signatures.
Gene set enrichment analysis showed that there was a highly significant overlap in the differentially expressed genes in the CHIKV arthritis model and in RA. This concordance also increased with the severity of RA, as measured by the inflammation score. A highly significant overlap was also seen between CHIKV arthritis and CIA. Pathway analysis revealed that the overlap between these arthritides was spread over a range of different inflammatory processes. Involvement of T cells and interferon-γ (IFNγ) in CHIKV arthritis was confirmed in studies of MHCII-deficient mice and IFNγ-deficient mice, respectively.
These results suggest that RA, a chronic autoimmune arthritis, and CHIKV disease, usually a self-limiting viral arthropathy, share multiple inflammatory processes. New drugs and biologic therapies being developed for RA may thus find application in the treatment of alphaviral arthritides.
基孔肯雅病毒（CHIKV）是一种由蚊子传播的甲病毒，可引发慢性致残性多关节痛/多关节炎，目前针对该疾病的治疗方法往往效果不佳。为评估正在研发的用于治疗类风湿性关节炎（RA）的新药是否可用于治疗甲病毒引起的关节炎，我们试图确定CHIKV关节炎的炎症基因表达特征是否与RA或胶原诱导的关节炎（CIA，一种RA的小鼠模型）存在相似之处。
我们利用最近在成年野生型小鼠中建立的CHIKV关节炎动物模型，生成了一个CHIKV关节炎基因表达特征共识，并用其查询公开可用的RA和CIA微阵列研究。然后使用重叠的基因特征进行通路分析。
基因集富集分析表明，CHIKV关节炎模型和RA中差异表达基因存在高度显著的重叠。这种一致性也随着RA严重程度的增加而增加，RA严重程度通过炎症评分衡量。CHIKV关节炎和CIA之间也存在高度显著的重叠。通路分析显示，这些关节炎之间的重叠分布在一系列不同的炎症过程中。分别在MHCII缺陷小鼠和IFNγ缺陷小鼠的研究中证实了T细胞和干扰素-γ（IFNγ）参与CHIKV关节炎。
这些结果表明，RA（一种慢性自身免疫性关节炎）和CHIKV疾病（通常是一种自限性病毒性关节病）共享多个炎症过程。因此，正在为RA研发的新药和生物疗法可能会应用于治疗甲病毒引起的关节炎。
