Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A subset of Hodgkin's disease (HD) patients have detectable Epstein-Barr virus (EBV) genomes in the malignant Reed-Sternberg (R-S) cells. R-S cells express only a limited set of latent EBV proteins, but only LMP1 and LMP2 can potentially elicit a CD8+ cytotoxic T-lymphocyte (CTL) response. We have evaluated if either of these proteins could be used as targets for specific adoptive T-cell therapy for EBV-positive (EBV+) HD. The success of this strategy requires that R-S cells are susceptible to lysis by CD8+ CTL, and that CTL specific for LMP1 and LMP2 can be detected and potentially amplified in HD patients. Antigen presentation and CTL sensitivity was evaluated with an in vitro maintained, phenotypically representative R-S cell line, HDLM-2. The R-S cells were able to process and present viral proteins, and to be efficiently lysed by specific CTL in a Class I-restricted manner. Since CTL responses to LMP1 and LMP2 do not represent the dominant responses to EBV, we examined if CTL clones specific for these proteins could be isolated despite the presence of weak or nondetectable responses in polyclonal T-cell lines. LMP-specific clones were generated from individuals either by cloning from the polyclonal EBV-reactive T-cell lines or by direct stimulation of peripheral blood mononuclear cells (PBMC) with cells expressing LMP1 or LMP2 as the only EBV protein. Our ability to isolate CTL specific for LMP proteins from individuals with HD and the sensitivity of R-S cells for CTL-mediated lysis suggest that the pursuit of specific adoptive immunotherapy represents a viable strategy for the subset of HD patients with EBV+ tumors.
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PMID:Isolation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes that lyse Reed-Sternberg cells: implications for immune-mediated therapy of EBV+ Hodgkin's disease. 905 19

To study the EBV DNA and expression of latent membrane protein I (LMP1) in patients with Hodgkin's disease from high incidence area of nasopharyngeal carcinoma, hot starting PCR and microwave treatment of LSAB immunohistochemistry methods were used to detect EBV DNA and LMP1 from biopsy specimens from 40 cases of Hodgkin's disease (HD) and 20 cases having benign lymph node lesions, randomly selected from a high incidence area of nasopharyngeal carcinoma. EBV DNA was detected in 65.0% of the HD cases and 50.0% of the benign lymph node cases, the difference was not of statistical significance. LMP1 of EBV was detected in 52.5% of HD cases and its expression was restricted to tumor cells. In addition, the detection rates of LMP1 and DNA of EBV in patients under 20 years of age (84.6% and 76.9% respectively) was much higher than that in patients over 20 years of age (56.0% and 40.0% respectively) P < 0.05. The results suggest that there was latent EBV infection in at least half of HD patients, which may have a role in the genesis and development of HD, and HD occurring in youth was more closely correlated with EBV latent infection and LMP1 expression.
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PMID:[The significance of detecting Epstein-Barr virus DNA and latent membrane protein I in Hodgkin's disease from a high incidence area of nasopharyngeal carcinoma]. 927 70

Previous studies have shown that in non-Hodgkin's lymphomas and others neoplasms, tumoral progression, treatment response, and outcome are related to the expression of different oncogenic and tumor suppressor proteins. This study aimed to determine the prognostic significance of the expression of p53, bcl2, retinoblastoma protein (Rb), Ki67, CD15, and latent membrane protein 1-Epstein-Barr Virus (LMP1-EBV) proteins in Hodgkin's disease. A retrospective study was performed on 140 patients collected at the 11 participating centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. A highly sensitive immunohistochemical method with previous microwave-induced antigen retrieval technique was used for the demonstration of the above-mentioned proteins. A Cox's multivariate analysis was performed to evaluate the impact of the variables in the overall survival, together with a logistic regression model for the achievement of complete remission. Univariate statistical analysis confirmed the prognostic significance of the alredy known clinical parameters: stage, age over 60 years, and B symptoms. High proliferation index (Ki67) and loss of Rb expression were also found to be adverse prognostic factors influencing respectively lower overall survival and failure to achieve complete remission. Multivariate analysis confirmed the independent significance of these two parameters and additionally identifies LMP1-EBV expression as a favorable prognostic marker, in relation with overall survival. Histopathological type, p53, bcl2, and CD15 expression lack significant influence on the outcome of this series. The progression of the disease or the response to treatment in HD patients is the consequence of the interrelationship of different factors, among which LMP1 expression, loss of Rb, and high growth fraction seems to play a more relevant role.
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PMID:Adverse clinical outcome in Hodgkin's disease is associated with loss of retinoblastoma protein expression, high Ki67 proliferation index, and absence of Epstein-Barr virus-latent membrane protein 1 expression. 931 Apr 94

Variable proportions of Hodgkin's disease (HD) cases are associated with the Epstein-Barr virus (EBV), but the role of EBV in HD is not entirely clear. Hodgkin and Reed-Sternberg (HRS) cells of EBV-associated HD are characterized by expression of the EBV gene product LMP1. In other cellular environments, LMP1 has been shown to induce interleukin (IL)-6. In this study, 105 HD cases were tested for differences in IL-6 expression among LMP1-positive and -negative cases. Isotopic in situ hybridization and correlation with the presence of EBV gene products revealed significantly higher proportions of cases with IL-6-expressing tumour cells in LMP1-positive (31 of 37, 84 per cent) as compared with LMP1-negative HD cases (35 of 68, 51 per cent). Thus, although not exclusive to EBV-positive HRS cells, IL-6 expression appears to be upregulated in EBV-associated HD. IL-6 receptor (CD126) expression was tested by in situ hybridization and found in a broad spectrum of cell types, regularly including HRS cells. Superinduction of IL-6 expression may be among the mechanisms by which EBV confers a growth advantage on virus-infected HRS cells and by which the virus may contribute to the morphological and clinical peculiarities of HD.
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PMID:Modulation of interleukin-6 expression in Hodgkin and Reed-Sternberg cells by Epstein-Barr virus. 934 32

A 61-year-old man with acquired immunodeficiency syndrome (AIDS) sought care because of the onset of progressive dysphagia. He was found to have a perforated, fungating esophageal mass. The combined histologic and immunologic findings were diagnostic of Hodgkin's disease, nodular sclerosis type, lymphocyte-depleted variant, arising in the esophagus. The Reed-Sternberg cells and mononuclear variants were positive for Epstein-Barr virus (EBV) latent membrane protein (LMP1) and EBV RNA. Occasional small lymphoid cells were also positive for EBV RNA. Polymerase chain reaction studies demonstrated the presence of EBV type A without deletion of the EBV LMP1 gene. Other authors have reported an increased frequency of type B EBV and deletion of the EBV LMP1 gene in cases of human immunodeficiency virus-associated Hodgkin's disease. Hodgkin's disease arising in the esophagus is rare in immunocompetent patients. However, in the presence of AIDS, Hodgkin's disease should be considered in the differential diagnosis of patients with signs or symptoms of esophageal disease.
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PMID:Hodgkin's disease of the esophagus. 935

Many aspects of Epstein-Barr virus (EBV) and tumor biology have been studied in Burkitt's lymphoma (BL)-derived cell lines. However, in tissue culture, patterns of gene expression and CpG [corrected] methylation often change and viral strain selection may occur. In this report, 10 cases of snap-frozen endemic BL tumors are characterized in terms of viral gene expression, promoter usage, methylation, and viral strain. EBNA1 and BamHI-A rightward transcripts (BART) were detected in 7 of 7 and LMP2A transcripts in 5 of 7 tumors with well-preserved RNA. Transcripts for the other EBNAs and for LMP1 were not detected in any tumor. These tumors differ from BL cell lines in that they lack a variety of lytic cycle transcripts. This pattern of viral gene expression in endemic BL is similar to that reported in peripheral blood mononuclear cells (PBMCs) from healthy EBV-seropositive individuals. EBNA1 transcripts originated from the Q promoter (Qp) but not C, W, or F promoters that drive transcription of EBNA1 in other circumstances. Whereas Cp has been previously shown to be entirely CpG methylated in BL, bisulfite genomic sequencing showed virtually no methylation in Qp. Type-A EBV was detected in 6 of 10 and type B in 4 of 10 cases. A previously reported 30bp deletion variant in the carboxyl terminal of LMP1 gene was detected in 5 of 10 cases. The association with both A and B strains contrasts with EBV-associated Hodgkin's disease, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disease, which are much more consistently associated with A strain virus.
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PMID:Epstein-Barr virus (EBV) in endemic Burkitt's lymphoma: molecular analysis of primary tumor tissue. 945 68

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) and latent membrane proteins (LMP) are the only antigens consistently expressed in malignancies such as nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD). Since EBNA1 is not recognized by EBV-specific cytotoxic T lymphocytes (CTL), there is increasing interest in the identification of the potential target epitopes within LMP1. Although LMP1-specific CTL have been isolated from seropositive individuals, earlier attempts to identify the peptide epitopes recognized by these T cells have been unsuccessful. In the present report we used a novel protocol to identify CTL epitopes within LMP1 which can be recognized by both polyclonal and clonal CTL. Firstly, a computer-based program was employed to identify the potential HLA-binding peptides within LMP1. Polyclonal CD8+ CTL were then isolated from seropositive donors that recognized the peptide epitopes YLLEMLWRL and YLQQNWWTL from LMP1 in association with HLA A2. Limiting dilution analysis of the memory CTL response revealed that the LMP1-specific CTL response constitutes a minor component of the CTL response in healthy virus carriers. Interestingly, analysis of YLLEMLWRL-specific CTL revealed that these CTL were able to lyse EBV-infected B cells expressing different HLA A2 supertype alleles including A*0201, A*0202, A*0203, A*0204, A*0206, A*6802 and A*6901. These data strongly support the notion that HLA class I supertype-restricted CTL may be of significant use in the development of peptide-based immunotherapeutics against EBV-associated malignancies in different ethnic populations.
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PMID:Identification of cytotoxic T cell epitopes within Epstein-Barr virus (EBV) oncogene latent membrane protein 1 (LMP1): evidence for HLA A2 supertype-restricted immune recognition of EBV-infected cells by LMP1-specific cytotoxic T lymphocytes. 952 Oct 52

Here we describe the case of a 14-year-old boy who underwent liver transplantation for post-Kasai biliary atresia when aged 4. Antirejection treatment consisted of prednisone and cyclosporine. At the age of 11 years the patient developed left cervical lymphadenopathy; the biopsy showed classical Hodgkin's disease(HD) of the mixed cellularity (MC) type. Neoplastic cells expressed CD30 and CD15, and were negative for CD45, CD20, CD3, CD43, and CD79a. Furthermore, they carried the EBV-related products LMP1 and EBER1/2. Treatment consisted of three cycles of adriamycin, bleomycin, vinblastine and DTIC (ABVD), followed by radiotherapy (2,000 cGys) on involved fields. At present, 42 months after the diagnosis of HD, the patient is still in complete remission. This is, to the best of our knowledge, the first reported case of classical HD following liver transplantation. The positivity of neoplastic cells for LMP1 and EBER1/2 indicates a possible role for immunosuppression in the development of the tumor, and whether a reduction in immunosuppression might have influenced the course of the disease is open to question.
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PMID:Hodgkin's disease occurring in a child after liver transplantation. 968 Oct 84

The Epstein-Barr virus (EBV)-encoded latent membrane proteins, LMP1 and LMP2, are consistently expressed by the malignant Hodgkin/Reed-Sternberg (HRS) cells of EBV-associated Hodgkin's disease (HD). Cytotoxic T lymphocyte (CTL) responses to both of these proteins have been shown in the blood of EBV-seropositive individuals, yet in HD the apparent failure of the CTL response to eliminate HRS cells expressing LMP1 and LMP2 in vivo has given rise to the suggestion that HD may be characterized by the presence of defects in antigen processing/presentation or in CTL function. This study has used immunohistochemistry to show high-level expression of major histocompatibility complex (MHC) class I molecules by the HRS cells of EBV-associated HD and either low level or absence of expression of MHC class I molecules on HRS cells of EBV-negative tumors. In addition, HRS cells expressed high levels of transporter-associated proteins (TAP-1, -2), irrespective of the presence of latent EBV infection. These results suggest that global downregulation of MHC class I molecules does not account for the apparent ability of EBV-infected HRS cells to evade CTL responses, but may be important in the understanding of EBV-negative disease. We have also sequenced an epitope in LMP2A (CLGGLLTMV) that is restricted through HLA A2.1, a relatively common allele in Caucasian populations, and showed that this epitope is wild type in a small group of EBV-associated HLA A2.1-positive HD tumors. This result may be relevant to proposed immunotherapeutic approaches for EBV-positive HD patients that target CTL epitopes.
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PMID:Analysis of major histocompatibility complex class I, TAP expression, and LMP2 epitope sequence in Epstein-Barr virus-positive Hodgkin's disease. 974 88

Nucleic acid sequence-based amplification (NASBA) assays were developed for direct detection of Epstein-Barr virus (EBV) transcripts encoding EBV nuclear antigen 1 (EBNA1), latent membrane proteins (LMP) 1 and 2, and BamHIA rightward frame 1 (BARF1) and for the noncoding EBV early RNA 1 (EBER1). The sensitivities of all NASBAs were at least 100 copies of specific in vitro-generated RNA. Furthermore, 1 EBV-positive JY cell in a background of 50,000 EBV-negative Ramos cells (the relative sensitivity) was detected by using the EBNA1, LMP1, and LMP2 NASBA assays. The relative sensitivity of the EBER1 NASBA was 100 EBV-positive cells, which was probably related to the loss of small RNA molecules during the isolation. The BARF1 and LMP2 NASBAs were evaluated on clinical material. BARF1 expression was found in 6 of 7 nasopharyngeal carcinomas (NPC) but in 0 of 22 Hodgkin's disease (HD) cases, whereas LMP2 expression was found in 7 of 7 NPCs and in 17 of 22 HD cases. For detection of EBNA1 transcripts in HLs (n = 12) and T- and B-cell non-Hodgkin's lymphomas (n = 3 and n = 2, respectively), NASBA was compared with reverse transcriptase (RT) PCR. Two samples were positive only with NASBA, and two other samples were positive only with RT-PCR; for all other samples, the RT-PCR and NASBA results were in agreement. We conclude that NASBA is suitable for sensitive and specific detection of the above-mentioned EBV transcripts, regardless of their splicing patterns and the presence of EBV DNA. The EBNA1, LMP2, and BARF1 NASBAs developed in this study proved to be reliable assays for detection of the corresponding transcripts in EBV-positive clinical material.
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PMID:Nucleic acid sequence-based amplification, a new method for analysis of spliced and unspliced Epstein-Barr virus latent transcripts, and its comparison with reverse transcriptase PCR. 977 58


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