Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children.
OBJECTIVE
The study goal was to determine the diagnostic accuracy of a specific cytokine pattern including interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-6 for hemophagocytic lymphohistiocytosis (HLH) in febrile children.


METHODS
In this prospective study, 756 patients with fever admitted to a hematology-oncology unit were enrolled. The causes of fever were documented and the serum cytokines, including IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-4, and IL-2, were determined using cytometric bead array techniques.


RESULTS
Of 1474 episodes of fever that were analyzed, 71 episodes of HLH manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 1088.5 pg/mL) and IL-10 (623.5 pg/mL) but a moderately increased level of IL-6 (51.1 pg/mL). IL-6 was predominantly increased to varied extents in patients in the sepsis group (244.6 pg/mL) and the nonsepsis infection group (34.7 pg/mL). The diagnostic accuracy of IFN-γ and IL-10 for HLH was 99.5% and 92.8%, respectively. By applying the cutoff point of 100 pg/mL, IFN-γ had a sensitivity of 94.4% and a specificity of 97.2% for HLH. When using the criteria of IFN-γ >75 pg/mL and IL-10 >60 pg/mL, the specificity reached 98.9% and the sensitivity was 93.0%.


CONCLUSIONS
The specific cytokine pattern of markedly elevated levels of IFN-γ and IL-10 with only modestly elevated IL-6 levels has high diagnostic accuracy for HLH and may be a useful approach to differentiate HLH from infection.
Children's Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Xiao-Jun
XJ
Xu
Yong-Min
YM
Tang
Hua
H
Song
Shi-Long
SL
Yang
Wei-Qun
WQ
Xu
Ning
N
Zhao
Shu-Wen
SW
Shi
He-Ping
HP
Shen
Jun-Qing
JQ
Mao
Ling-Yan
LY
Zhang
Bin-Hua
BH
Pan
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000175:diagnosis*; D008297:Male; D011446:Prospective Studies; D015203:Reproducibility of Results; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma