Evaluation of Th1/Th2 cytokines as a rapid diagnostic tool for severe infection in paediatric haematology/oncology patients by the use of cytometric bead array technology

Abstract

Haematology/oncology children are usually at risk for various infections after intensive chemotherapy. We evaluated the quantification of Th1/Th2 cytokines with a flow cytometric bead array (CBA) in 795 hospitalized haematology/oncology children (309 febrile and 486 afebrile patients) to seek for a diagnostic method for determination of the type and the severity of infection. Three hundred and nine febrile patients developed a total of 505 febrile episodes. Microbiological examination demonstrated a positive blood culture (microbiologically documented infection (MDI)) in 145/505 febrile episodes. The controls included 550 healthy children, 43 haemophagocytic lymphohistiocytosis (HLH) patients, 35 cytomegalovirus infection patients and 19 Epstein-Barr virus infection patients. Interleukin (IL)-4, IL-6, IL-10, tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in febrile episodes were significantly higher than those in healthy children, and the cytokine profile was different from that of the HLH controls or the viral infection controls. IL-6 levels were much higher in MDI patients (usually >1000.0 pg/mL, 60/145) than in HLH patients (2/43); however, IFN-γ levels were only slightly increased in MDI patients, rarely being more than 100.0 pg/mL (8/145 vs. 39/43 in HLH patients). The median levels of IL-4, IL-6, IL-10, TNF-α and IFN-γ in febrile patients before antibiotic therapy were 3.9, 660.1, 122.7, 6.9 and 11.4 pg/mL, respectively, and returned to 3.3, 22.8, 9.6, 4.1 and 6.4 pg/mL, respectively, after infection was controlled. IL-6 and IL-10 levels were positively associated with septic shock and mortality rates. In conclusion, our results have demonstrated the usefulness of IL-6/IL-10/TNF-α/IFN-γ determination with CBA technology for the early rapid diagnosis, severity evaluation and assessment of therapy effect in febrile haematology/oncology children.

Pathogenesis of bloodstream infection in children with blood cancer

“…The basic diseases of the BSI patients consisted of 112 cases of acute lymphocytic leukemia, 34 of acute myelogenous leukemia, 10 of lymphoma, 4 of hemophagocytic syndrome and 1 of Langerhans cell histiocytosis. The etiologically diagnosed patients with positive blood culture were categorized as the microbiologically documented infection (MDI) group and the clinically diagnosed patients with negative blood culture were the non-MDI group (6,7). The study was approved by the ethics committee of the Children’s Hospital affiliated to the School of Medicine of Zhejiang University, and written, informed consent was obtained from the patients’ parents or legal guardians in all cases.…”

IP-10/CXCL10 and MIG/CXCL9 as novel markers for the diagnosis of lymphoma-associated hemophagocytic syndrome

“…ELISA is time-consuming and expensive, and requires a large amount of serum. In recent years, a newly developed technique, cytometric bead array (CBA) [23–27], has been introduced in the field of clinical medicine [19, 28–32]. This assay system has resolved the majority of faults of ELISA.…”

Novel Mutations in the UNC13D Gene Carried by a Chinese Neonate with Hemophagocytic Lymphohistiocytosis

“…A specific Th1/Th2 cytokine pattern to diagnose HLH was first reported by our group with excellent clinical application 12,13. During the acute phase of HLH without complicating bacterial infection, both IFN-γ and IL-10 levels should be increased, while IL-6 remains normal or only slightly elevated.…”

“…When HLH patients enters remission, the levels of IFN-γ and IL-10 both decline, usually with IFN-γ declining faster than IL-10. According to our previous studies, IL-6 levels are much higher in microbiologically documented infection patients than in patients with non-sepsis 13. When IFN-γ, IL-10 and IL-6 levels return to normal or close to normal, the HLH related conditions of the patient can be considered to be in control.…”