Cytokine profiles as novel diagnostic markers of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children.

PURPOSE: The aim of this study was to identify specific laboratory indices to distinguish Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children. MATERIALS AND METHODS: In this prospective study, Th1/Th2 cytokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were analyzed in patients with EBV-HLH or sepsis at the onset of disease by flow cytometry. RESULTS: IL-10, IFN-γ, IL-10/IL-6, and IFN-γ/IL-6 were higher and IL-6 was lower in EBV-HLH patients compared to sepsis patient levels. When using the criteria of IL-10 >20.9 pg/mL, IFN-γ >17.9 pg/mL, IL-10/IL-6 >0.5 and IFN-γ/IL-6 >0.7, the sensitivity was 89.8%, 93.2%, 93.2%, and 91.5%, while the specificity was 89.8%, 100%, 94.9%, and 100%, respectively. After treatment of EBV-HLH patients, IL-6, IL-10, TNF-α, and IFN-γ were significantly reduced (IL-6: P<.001; IL-10: P<.001; TNF-α: P=.011; IFN-γ: P<.001). CONCLUSIONS: This study showed that IFN-γ, IL-10/IL-6, and IFN-γ/IL-6 are novel specific indicators for differential diagnosis of EBV-HLH. Additionally, IL-6, IL-10, TNF-α, and IFN-γ are useful indices for monitoring the effects of treatment on EBV-HLH.

Characterization of microRNAs expression profiling in one group of Chinese urothelial cell carcinoma identified by Solexa sequencing.

OBJECTIVE: The goal of this study was to extend the known repertoire of microRNAs (miRNAs) expressed in urothelial bladder cancer (BCa) of the Chinese population and further understand the molecular events of miRNAs underlying urothelial bladder tumorigenesis at the global genome level. MATERIALS AND METHODS: We separated well-characterized epithelial tumor cells from 20 moderately differentiated or poorly differentiated BCa specimens by laser capture microdissection (LCM) and pooled these cells of interest prior to RNA analysis. Ten normal bladder epithelia (NBE) samples were pooled as the control. After preparation of small RNAs library, the 2 samples were sequenced simultaneously by the next generation high through-put Solexa sequencing technology. RESULTS: We employed the next generation high through-put Solexa sequencing technology to clone and identify miRNAs in BCa and NBE, and generated 11,146,610, and 10,263,845 high quality sequence reads, respectively. According to the analysis of size distribution, 22 nt class was the most abundant group of small RNAs in the BCa. Likewise, the 20 and 22 nt sequences were significantly greater than shorter or longer sequences, and accounted for 59.55% of the total sequence number of NBE library. The whole-genome-scale data mining suggested that BCa and NBE libraries both contained multiple and heterogeneous small RNA species. On further analysis, the sequencing data revealed that different miRNAs showed clearly in-house differential expression levels in BCa and NBE and 74 miRNAs aberrantly expressed between BCa and NBE at the global genome level. We also predicted 13 novel miRNAs in both BCa and NBE libraries. CONCLUSIONS: Our results suggest that BCa miRNAs include a large proportion of conserved miRNAs and a set of non-conserved miRNAs with low expression levels. These known and newly identified miRNAs at the population level significantly enhance our knowledge of BCa miRNAs expression profiling and provide insights into miRNAs oncogenesis and oncotherapy in BCa. Further studies are necessary to elucidate the roles of miRNAs in urothelial bladder tumorigenesis and determine the potential of miRNAs as diagnostic and prognostic tools or therapeutic targets for BCa in the future.