title: [Diagnostic significance of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis].
abstract: OBJECTIVE
  To illustrate the diagnostic value of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis (HLH) and its diagnostic accuracy.
  
  
  METHODS
  The BD(TM) CBA Human Th1/Th2 Cytokine Kit II was used to measure the serum Th1 and Th2 cytokines, including Interferon-gamma (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-10, IL-6, IL-4 and IL-2 in 50 patients with de novo HLH admitted to our hospital from Oct. 2005 to Aug. 2009. The above cytokine levels were also determined in 250 healthy volunteers and 235 patients with sepsis as controls.
  
  
  RESULTS
  The primary features of these patients were prolonged high-grade fever (50/50), hepatomegaly (44/50), splenomegaly (38/50), hemocytopenia (47/50), hyperferritinemia (49/50), coagulopathy (44/50), hemophagocytosis in bone marrow (42/50), liver dysfunction (42/50) and hypertriglyceridemia (42/50). The IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 levels for healthy children were (4.6 ± 1.8) ng/L, (4.0 ± 1.2) ng/L, (6.5 ± 1.3) ng/L, (6.0 ± 1.5) ng/L, (2.9 ± 0.8) ng/L and (2.6 ± 0.7) ng/L, while the median levels of them in acute phase of HLH children were 1138.5 (49.2 - 5000.0) ng/L, 3.4 (1.0 - 25.1) ng/L, 740.5 (26.5 - 5000.0) ng/L, 66.1 (3.9 - 4472.6) ng/L, 3.9 (1.0-32.8) ng/L and 4.0 (1.0 - 51.1) ng/L, respectively. The cytokine levels decreased to 9.1 (1.9 - 180.1) ng/L, 2.9 (1.0 - 11.0) ng/L, 11.4 (2.9 - 184.2) ng/L, 6.5 (1.0 - 44.8) ng/L, 2.7 (1.0 - 6.5) ng/L and 4.1 (1.0 - 12.0) ng/L respectively after remission. The IFN-γ, IL-10 and IL-6 levels in acute phase were significantly higher than those after remission and those of the healthy control (P all < 0.001). IL-4, IL-2 and TNF slightly elevated or at normal range in acute phase of HLH. The patients with sepsis showed a different cytokine pattern, with an extremely high level of IL-6 (median: 251.3 ng/L, range: 8.4- > 5000.0 ng/L) and moderately elevated level of IL-10 (median: 46.5 ng/L, range: 3.1 - 5000.0 ng/L), whereas IFN-γ was only slightly elevated (median: 9.2 ng/L, range: 1.3 - 498.8 ng/L). When the criteria for HLH set as the following: IFN-γ > 100 ng/L, IL-10 > 60 ng/L and the concentration of IFN-γ higher than that of IL-6, the specificity reached as high as 98.7% and the sensitivity was 88.0% for the diagnosis of HLH among patients with HLH and sepsis. Meanwhile, the positive predictive value (PPV) and negative predictive value (NPV) could reach 93.6% and 97.5%, respectively.
  
  
  CONCLUSIONS
  The significant increase of IFN-γ and IL-10 with slightly increased level of IL-6 is a sensitive and specific cytokine pattern for childhood HLH, which is helpful for its diagnosis and differential diagnosis.
authors.affiliation: Division of Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Xu
authors.forename: Yong-min
authors.initials: YM
authors.lastname: Tang
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.forename: Hua
authors.initials: H
authors.lastname: Song
authors.forename: Shi-long
authors.initials: SL
authors.lastname: Yang
authors.forename: Shu-wen
authors.initials: SW
authors.lastname: Shi
authors.forename: Wei-qun
authors.initials: WQ
authors.lastname: Xu
authors.forename: Bin-hua
authors.initials: BH
authors.lastname: Pan
authors.forename: Ling-yan
authors.initials: LY
authors.lastname: Zhang
authors.forename: Jun-qing
authors.initials: JQ
authors.lastname: Mao
authors.forename: He-ping
authors.initials: HP
authors.lastname: Shen
authors.forename: Min-er
authors.initials: ME
authors.lastname: Gu
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000175:diagnosis*; D008297:Male; D012680:Sensitivity and Specificity; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma