A Non-invasive Diagnosis of Histiocytic Necrotizing Lymphadenitis by Means of Gene Expression Profile Analysis of Peripheral Blood Mononuclear Cells
A Non-invasive Diagnosis of Histiocytic Necrotizing Lymphadenitis by Means of Gene Expression Profile Analysis of Peripheral Blood Mononuclear Cells
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DOI：
10.1007/s10875-013-9897-y
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发表时间：
2013-07-01
影响因子：
9.1
通讯作者：
Hara, Toshiro
中科院分区：
文献类型：
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作者：
Ishimura, Masataka;Yamamoto, Hiroyuki;Hara, Toshiro
组织细胞坏死性淋巴结炎（HNL），也称为菊池-藤本病，是一种良性、自限性的炎症性疾病，伴有发热和疼痛的颈部淋巴结病，病因不明。由于HNL没有特异性症状或实验室检查结果，因此需要进行淋巴结活检以进行明确诊断。为了建立快速、无创的诊断方法，本研究利用外周血单个核细胞（PBMC）基因芯片技术，通过全基因组转录分析，研究了患者特异性表达的基因。HNL中表达上调的前5个基因（IFI 44 L、CXCL 10、GBP 1、EPSTI 1和IFI 27）均为干扰素诱导基因（ISG）。通过定量PCR验证芯片表达上调基因的表达水平。高水平的血清CXCL 10浓度被证实在HNL患者的症状阶段。这5个基因的表达水平之间呈正相关（r（2）=0.28-0.60）。这些基因在HNL淋巴结中也有高表达。使用这五个基因的表达水平的判别分析以84%的准确度区分HNL。HNL中上调的ISG的组合似乎是由病毒感染或自身抗原诱导的特异性应答。PBMC基因表达谱分析可为HNL的快速无创诊断提供依据。
Histiocytic necrotizing lymphadenitis (HNL), also called Kikuchi-Fujimoto disease, is a benign, self-limiting inflammatory disease with fever and painful cervical lymphadenopathy of unknown etiology. A lymph node biopsy is required for the definitive diagnosis because of no specific symptoms or laboratory findings for HNL. To establish the rapid non-invasive diagnostic method for this disease, we investigated genes specifically expressed in the patients by analyzing whole transcriptome using microarray analysis of peripheral blood mononuclear cells (PBMC). The top five upregulated genes (IFI44L, CXCL10, GBP1, EPSTI1 and IFI27) in HNL were interferon-induced genes (ISGs). The expression levels of the up-regulated genes by microarray were verified by quantitative PCR. High levels of serum CXCL10 concentration were confirmed at the symptomatic phase of HNL patients. The expression levels of these 5 genes positively correlated with each other (r(2)=0.28-0.60). The genes were also highly expressed in HNL lymph nodes. The discriminant analysis using the expression levels of these five genes distinguished HNL with 84 % accuracy. The combination of upregulated ISGs in HNL seemed to be a specific response induced by viral infections or autoantigens. An analysis of the gene expression profile of PBMC may provide a rapid non-invasive diagnosis of HNL.