separation-immune-cell-subpopulations-peripheral-blood-samples-from

Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis

Infectious mononucleosis (IM) is an acute syndrome mostly associated with primary Epstein&#8211;Barr virus (EBV) infection. The main clinical symptoms ...

Capital Medical University, National Center for Children's Health

Chinese Academy of Medical Sciences

In China, primary EBV infection occurs during childhood with seroprevalence reaching about 100% by 10 years of age. There are few studies on EBV variants in diseases associated with EBV infection in Chinese children. In this study, we investigated the diversity of the EBV genes (EBNA-1 and LMP-1) and the relationship between EBV variants and the clinical phenotypes in diseases associated with EBV infections in Chinese pediatric cases.

Analysis of EBNA-1 and LMP-1 variants in diseases associated with EBV infection in Chinese children.

Epstein-Barr virus associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a high mortality rate among children. The pathogenesis of, and underlying predisposing factors for, EBV-HLH are as yet unclear; however, natural killer cells may play a key role in progression of the disease. This study attempted to determine whether killer cell immunoglobulin-like receptor (KIR) gene polymorphisms are responsible for susceptibility to EBV-HLH. Of the 125 children with EBV infection studied, 59 had EBV-HLH and 66 patients had EBV associated infectious mononucleosis (IM) without HLH. The control group was 146 normal children without immune deficiency. KIR polymorphisms were determined by polymerase chain reaction with sequence-specific primers. KIR polymorphism data were analyzed using the X(2) test or Fisher's exact test. The overall observed carrier frequency (OF) of KIR2DS5 was significantly higher in EBV-HLH patients than in IM patients and normal controls (49.2% versus 31.8%, P = 0.048; 49.2% versus 31.5%, P = 0.018, respectively), and the odds ratios (95% confidence interval) were 2.071 (1.001-4.286) and 2.101(1.132-3.900) respectively. The OF of KIR3DS1 was significantly higher in the EBV-HLH patients than in the IM patients (47.4% versus 24.6%, P = 0.012), but not different from normal controls. In summary, KIR polymorphisms may be involved in the development of EBV-HLH, with KIR2DS5 promoting susceptibility to this disease. The obtained KIR data will enrich the understanding of genetic relationships among diseases associated with EBV infection in children.

Killer cell immunoglobulin-like receptor gene polymorphisms predispose susceptibility to Epstein-Barr virus associated hemophagocytic lymphohistiocytosis in Chinese children.

The aim of this study is to investigate the relationship between cytokine gene polymorphisms and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children, and to further reveal the possible mechanisms of EBV-HLH.

IL-10-592 A/C polymorphisms is associated with EBV-HLH in Chinese children.

OBJECTIVE To investigate the distribution of killer cell immunoglobulin-like receptors (KIR) and their specific ligands human leukocyte antigen-I (HLA-I) gene in northern China. METHODS One hundred and eighty-four unrelated northern Chinese Han individuals were recruited. Genotypes of the KIR and HLA-ABC genes were studied by sequence-specific primer polymerase chain reaction (SSP-PCR). RESULTS Sixteen KIR genes were detected among the 184 unrelated individuals. In all individuals, the four framework genes were present. The frequencies for those carrying the remaining 12 KIR genes have ranged from 16.3% to 99.5%. Twenty-four KIR genotypes were identified, for which half were detected in a single individual. A new genotype comprised of KIR2DL3, 3DL1, 2DP1 and the framework genes was detected in one subject. Respectively, 12, 27 and 11 specificities of HLA alleles were identified on the HLA-A, B, C loci. CONCLUSION The distribution of polymorphisms of KIR and its ligand HLA-ABC genes among northern Chinese Han population have been ascertained. The frequencies of 9 KIR/HLA combinations in the above population have been determined for the first time.

[Polymorphisms of killer cell immunoglobulin-like receptor and its ligand HLA-I gene among northern Chinese Han population].

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening complication of EBV infection. MicroRNAs (miRNAs) were small non-coding RNA, and EBV could encode miRNAs that are involved in the progression of infection. However, the profiles of EBV-miRNAs in EBV-HLH were unknown. Here, we aimed to profile the expression of EBV-miRNAs in children with EBV-HLH by analyzing 44 known EBV-miRNAs, encoded within the BamHI fragment H rightward open reading frame 1 (BHRF1) and the BamHI-A region rightward transcript (BART), in plasma and cellular targets by real-time quantitative PCR. The study included 15 children with EBV-HLH, 15 children with infectious mononucleosis (IM), and 15 healthy controls. CD8(+) T cells were found to be the cellular target of EBV infection in EBV-HLH, while CD19(+) B cells were infected with EBV in IM. We also found the greater levels of several miRNAs encoded by BART in EBV-HLH, compared to those in IM and healthy controls, whereas the levels of BHRF1 miRNAs were lower than those in IM. The profile and pattern of EBV-miRNAs in EBV-HLH indicated that EBV could display type II latency in EBV-HLH. Importantly, the level of plasma miR-BART16-1 continued decreasing during the whole chemotherapy, suggesting that plasma miR-BART16-1 could be a potential biomarker for monitoring EBV-HLH progression. The pathogenesis of EBV-HLH might be attributed to the abundance of EBV-miRNAs in EBV-HLH. These findings help elucidate the roles of EBV miRNAs in EBV-HLH, enabling the understanding of the basis of this disease and providing clues for its treatment.

Profiling of EBV-Encoded microRNAs in EBV-Associated Hemophagocytic Lymphohistiocytosis.

Epstein-Barr virus (EBV) was the first virus identified to encode microRNAs (miRNAs). Both of viral and human cellular miRNAs are important in EBV infection. However, the dynamic expression profile of miRNAs during primary EBV infection was unknown. This study aimed to investigate the dynamic expression profile of viral and cellular miRNAs in infectious mononucleosis (IM) caused by primary EBV infection.

Dynamic expression of viral and cellular microRNAs in infectious mononucleosis caused by primary Epstein-Barr virus infection in children.

In China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute viral encephalitis and meningitis in Chinese children.

Article	Year
Analysis of EBNA-1 and LMP-1 variants in diseases associated with EBV infection in Chinese children. Virology journal\| PubMed ID: 22236445	2012
Killer cell immunoglobulin-like receptor gene polymorphisms predispose susceptibility to Epstein-Barr virus associated hemophagocytic lymphohistiocytosis in Chinese children. Microbiology and immunology\| PubMed ID: 22376216	2012
IL-10-592 A/C polymorphisms is associated with EBV-HLH in Chinese children. Hematology (Amsterdam, Netherlands)\| PubMed ID: 26222684	2016
[Polymorphisms of killer cell immunoglobulin-like receptor and its ligand HLA-I gene among northern Chinese Han population]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics\| PubMed ID: 26418984	2015
Profiling of EBV-Encoded microRNAs in EBV-Associated Hemophagocytic Lymphohistiocytosis. The Tohoku journal of experimental medicine\| PubMed ID: 26423217	2015
Dynamic expression of viral and cellular microRNAs in infectious mononucleosis caused by primary Epstein-Barr virus infection in children. Virology journal\| PubMed ID: 26634702	2015
Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study. BMC infectious diseases\| PubMed ID: 28705180	2017

Junhong Ai

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