Study of biomarker and pathophysiology in non-hereditary periodic fever syndrome

基因芯片和定量RT-PCR结果显示，PFAPA综合征发热期CXCL10、ANKRD22、SERPING1、SLAMF8、GBP1mRNA表达水平明显高于非发热期、正常对照组和疾病对照组。在炎性标志物的定量方面，单核细胞CD64表达在发热期升高。单核细胞来源的趋化因子CXCL9在PFAPA综合征发热期的血清水平高于腺病毒感染期。鉴于这些发现提示单核细胞的激活在PFAPA综合征的病理生理过程中起着重要作用，我们用单核细胞白血病细胞系THP-1进行了体外实验。THP-1细胞经脂多糖刺激后，定量RT-PCR显示CXCL10和GBP1的表达增加，提示这些分子在PFAPA综合征单核细胞的天然免疫反应中起关键作用。

Febrile period of PFAPA syndrome showed increased mRNA expression of CXCL10, ANKRD22, SERPING1, SLAMF8, GBP1 by microarray and quantitative RT-PCR, compared to non-febrile period of PFAPA syndrome, normal controls and disease controls. In quantification of inflammatory markers, CD64 expression on monocytes was increased in febrile period of PFAPA syndrome. Serum level of CXCL9, a monocyte-derived chemokine, was higher in febrile period of PFAPA syndrome than in adenovirus infection. As these findings suggested that activation of monocytes plays important role in the pathophysiology of PFAPA syndrome, in vitro assay using THP-1 cells, a monocytic leukemia cell line, was performed. Quantitative RT-PCR of THP-1 cells showed increased expression of CXCL10 and GBP1 after stimulation by LPS, suggesting that these molecules play pivotal role in innate immune response of monocytes in PFAPA syndrome.