Patients with chronic active EBV infection each had two to five different LMP1 nucleotide sequences, whereas patients with infectious mononucleosis each had one to seven different sequences.
Overall, these data suggest that immunotherapy targeting LMP1 in EBV-associated NK lymphomas and CAEBV might serve as an alternative treatment modality.
We analysed the 30-bp deletion and the single-base mutations of the LMP-1 gene in 13 spontaneously established lymphoblastoid cell lines (LCLs) from peripheral blood mononuclear cells of three healthy children, four patients with EBV-unrelated acute febrile illnesses, three patients with infectious mononucleosis (IM), and three patients with chronic active EBV infection (CEBV), and six frozen samples from four patients with CEBV and two patients with EBV-associated hemophagocytic syndrome (EBV-AHS).
These results suggest that CAEBV T-cells are activated to transcribe IFN gamma, IL-10, and TGF beta excessively, and the latter two genes are expressed preferentially in the EBV-infected subsets.
Because continued EBV replication could allow for increased vIL-10, ELISA and immunoprecipitation were used to determine whether vIL-10 expression during chronic active EBV infection resulted in vIL-10 and IL-10 antibodies.
The harbored mutations were mainly in epigenetic modifiers, JAK-STAT signaling pathway, and apoptosis/cell cycle pathway, including SOCS1, DDX3X, and KMT2D, similar to other EBV-associated T/NK-cell lymphoproliferative disorders.
Here, we show that CAEBV originates from an EBV-infected lymphoid progenitor that acquires DDX3X and other mutations, causing clonal evolution comprising multiple cell lineages.
Pathways promoting proliferation, such as Janus associated kinase/ Signal Transducer and Activator of Transcription (JAK/STAT) and nuclear factor kB, are upregulated in ENKTL while upregulation of survivin and deregulation of p53 inhibit apoptosis in both ENKTL and chronic active EBV infection (CAEBV).
Primary acute or chronic active Epstein-Barr virus infection triggers EBV+ T-LPD's onset and the disease involves clonal proliferation of infected T-cells with activated cytotoxic phenotype.
Primary acute or chronic active Epstein-Barr virus infection triggers EBV+ T-LPD's onset and the disease involves clonal proliferation of infected T-cells with activated cytotoxic phenotype.
Moreover, the unique up-regulation of CD64A/B and its significant correlation with the monocyte marker CD14 was observed in CAEBV and that implies an important role of monocytes in CAEBV.
Moreover, the unique up-regulation of CD64A/B and its significant correlation with the monocyte marker CD14 was observed in CAEBV and that implies an important role of monocytes in CAEBV.
Here we report a patient with prolonged severe CAEBV who underwent bone marrow transplant for his disease and subsequently was found to have compound heterozygous mutations in STXBP2 (MUNC18-2) as well as a heterozygous mutation in PRF1 (perforin 1).
Here we report a patient with prolonged severe CAEBV who underwent bone marrow transplant for his disease and subsequently was found to have compound heterozygous mutations in STXBP2 (MUNC18-2) as well as a heterozygous mutation in PRF1 (perforin 1).
Two upregulated genes, RIPK2 and CDH9, were identified as common specific markers for chronic active EBV infection in both in vitro and in vivo studies.
Two upregulated genes, RIPK2 and CDH9, were identified as common specific markers for chronic active EBV infection in both in vitro and in vivo studies.
Three cell clones, SNK-1, -3 and -6, were derived from patients with nasal T/NK-cell lymphomas; two cell clones, SNK-5 and -10, were isolated from patients with chronic active EBV infection (CAEBV); and the other cell clone, SNK-11, was from a patient with hydroa vacciniforme (HV)-like eruptions.
Reduction of the Th1-type cytokine interferon gamma (IFN-gamma) in CAEBV was confirmed by Reverse transcriptase-polymerase chain reaction, whereas IFN-gamma expression was markedly enhanced in NKL, and moderately enhanced in IM.
Four novel Epstein-Barr virus (EBV)-carrying T-cell lines, designated SIS, AIK-T8, AIK-T4, and SKN, were established from peripheral blood lymphocytes (PBL) of patients with severe chronic active EBV infection, in the presence of interleukin-2 and 4-deoxyphorbol ester.