title: A non-invasive diagnosis of histiocytic necrotizing lymphadenitis by means of gene expression profile analysis of peripheral blood mononuclear cells.
abstract: 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 up-regulated 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 up-regulated 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.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan. ischii@pediatr.med.kyushu-u.ac.jp
authors.forename: Masataka
authors.initials: M
authors.lastname: Ishimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yumi
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takada
authors.forename: Motohiro
authors.initials: M
authors.lastname: Goto
authors.forename: Takehiko
authors.initials: T
authors.lastname: Doi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hoshina
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000293:Adolescent; D001681:Biological Assay; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020042:Histiocytic Necrotizing Lymphadenitis / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D059467:Transcriptome; D015854:Up-Regulation