Journal of Clinical Immunology

, Volume 33, Issue 5, pp 1018–1026 | Cite as

A Non-invasive Diagnosis of Histiocytic Necrotizing Lymphadenitis by Means of Gene Expression Profile Analysis of Peripheral Blood Mononuclear Cells

  • Masataka IshimuraEmail author
  • Hiroyuki Yamamoto
  • Yumi Mizuno
  • Hidetoshi Takada
  • Motohiro Goto
  • Takehiko Doi
  • Takayuki Hoshina
  • Shouichi Ohga
  • Koichi Ohshima
  • Toshiro Hara
Original Research


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 (r2 = 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.


Histiocytic necrotizing lymphadenitis Kikuchi-Fujimoto disease interferon-stimulated genes gene expression discriminate analysis 



Beta actin




Area under the curve


Complementary DNA


Threshold cycle


Chemokine (C-X-C motif) ligand 10


Epithelial stromal interaction 1 (breast)


Influenza type A virus


Guanylate binding protein 1 interferon-inducible


Histiocytic necrotizing lymphadenitis




Interferon alpha-inducible protein 27


Interferon-induced protein 44-like




Infectious mononucleosis


Interferon-stimulated gene


Kawasaki disease


Purulent lymphadenitis


Peripheral blood mononuclear cells


Polymerase chain reaction


Systemic lupus erythematosus


Systemic onset juvenile idiopathic arthritis



We thank Department of Pathology, Faculty of Medicine, Fukuoka University, Japan, for the material support. The statistical analyses were advised by Junji Kishimoto at Kyushu University Hospital, Japan. This work was supported by a Grant-in-Aid for research on intractable diseases for Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Masataka Ishimura
    • 1
    Email author
  • Hiroyuki Yamamoto
    • 1
  • Yumi Mizuno
    • 2
  • Hidetoshi Takada
    • 1
  • Motohiro Goto
    • 1
  • Takehiko Doi
    • 1
  • Takayuki Hoshina
    • 1
  • Shouichi Ohga
    • 1
    • 3
  • Koichi Ohshima
    • 4
  • Toshiro Hara
    • 1
  1. 1.Department of Pediatrics, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Fukuoka Children’s Hospital and Medical Center for Infectious DiseasesFukuokaJapan
  3. 3.Department of Perinatal and Pediatric Medicine, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  4. 4.Department of Pathology, School of MedicineKurume UniversityKurumeJapan

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