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Sheng L, Zhang W, Gu J, Shen K, Luo H, Yang Y. Novel mutations of STXBP2 and LYST associated with adult haemophagocytic lymphohistiocytosis with Epstein-Barr virus infection: a case report. BMC MEDICAL GENETICS 2019; 20:34. [PMID: 30782130 PMCID: PMC6379998 DOI: 10.1186/s12881-019-0765-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 02/13/2019] [Indexed: 12/15/2022]
Abstract
Background Haemophagocytic lymphohistiocytosis is a life-threatening disease resulting from primary or secondary hyper-inflammatory disorders. The typical symptoms include persistent fever, splenomegaly, cytopenia and significant elevation of serum ferritin. Case presentation We report a 30-year-old Chinese female patient who was diagnosed with chronic active Epstein-Barr virus infection more than 9 months prior and has since been presenting with cutaneous lymphoproliferative disorders mimicking hydroa vacciniforme and subsequent haemophagocytic lymphohistiocytosis. Exome sequencing suggested novel digenic heterozygous STXBP2 (c.592A > C, p.Thr198Pro) and LYST (c.830A > T, p.His277Leu) mutations. Conclusions This is the first case report in which adult HLH was associated with novel digenic mutations of STXBP2 and LYST combined with Epstein-Barr virus infection. It could also be the first polygenic model report, given that the pathogenicity of other mutated genes still remains unclear. We additionally conducted an in-depth, two-generation pedigree analysis to further illustrate the mode of inheritance in this case.
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Affiliation(s)
- Lingshuang Sheng
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Wei Zhang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Jia Gu
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Kefeng Shen
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Hui Luo
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Yang Yang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
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Successful resolution of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis during the treatment course of acute lymphoblastic leukemia. Pediatr Neonatol 2017; 58:555-557. [PMID: 28579038 DOI: 10.1016/j.pedneo.2016.11.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 10/04/2016] [Accepted: 11/04/2016] [Indexed: 11/20/2022] Open
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3
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Haverkos BM, Huang Y, Gru A, Pancholi P, Freud AG, Mishra A, Ruppert AS, Baiocchi RA, Porcu P. Frequency and clinical correlates of elevated plasma Epstein-Barr virus DNA at diagnosis in peripheral T-cell lymphomas. Int J Cancer 2017; 140:1899-1906. [PMID: 27943278 DOI: 10.1002/ijc.30566] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 10/19/2016] [Accepted: 11/14/2016] [Indexed: 12/11/2022]
Abstract
Epstein-Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients. Fifteen of 61 patients (24.5%, 95% CI: 14-37%) were pre-treatment pEBVd+, with no significant differences in baseline characteristics or treatment between pEBVd+ and pEBVd- patients. EBER-ISH was performed on 10 pEBVd+ and 35 pEBVd- tumors. All 10 pEBVd+ patients were EBER+, but 9 pEBVd- patients were also EBER+. With median follow up of 24 months (range 1-96), overall survival (OS) was shorter in pEBVd+ compared to pEBVd- patients (13 vs. 72 months; p = 0.04). In our retrospective study, pre-treatment pEBVd was elevated in 25% of PTCL patients, was highly specific for EBER+ tumors, and was associated with shorter survival. pEBVd should be further explored as a prognostic variable and tumor biomarker in PTCL.
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Affiliation(s)
| | - Ying Huang
- Division of Hematology, The Ohio State University, Columbus, OH
| | - Alejandro Gru
- Department of Pathology, University of Virginia, Charlottesville, VA
| | - Preeti Pancholi
- Department of Pathology, The Ohio State University, Columbus, OH
| | - Aharon G Freud
- Department of Pathology, The Ohio State University, Columbus, OH.,Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH
| | - Anjali Mishra
- Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH
| | - Amy S Ruppert
- Division of Hematology, The Ohio State University, Columbus, OH
| | - Robert A Baiocchi
- Division of Hematology, The Ohio State University, Columbus, OH.,Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH
| | - Pierluigi Porcu
- Division of Hematology, The Ohio State University, Columbus, OH.,Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH
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4
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Abstract
Half a century has passed since Epstein-Barr virus (EBV) particles were isolated from the cultured lymphoblasts of Burkitt lymphoma. During the period, molecular biology, hematology/immunology, and transplantation medicine made amazing progress, that clarified the mode of infection and pathophysiology of the virus in human diseases. Research strategies on the relationship between EBV and human have expanded to the epidemiology, structures and functions of both genomes, regulatory genes including microRNA, and the nature of epigenetics. Although no animal models of EBV infection long hampered the completion of in vivo experiments, humanized mice have broken through a barrier of in vitro study on EBV-infected cell lines. Our understanding of the life cycle of EBV has continued to deepen about the infection via the CD21 receptor expressed on B cells, the latency, reactivation/reinfection, and transformation, and also the dynamics of T-cell immune response and the intracellular immunosurveillance beyond acquired and innate immunity. On the other hand, the disease entity of life-threatening lymphoproliferative disease of EBV-infected T cells or NK cells is on controversial. The other parts of this special issue include the recent topics of the basic and clinical researches of EBV as the oncogenic virus. Then, we herewith overview the research history of EBV with special reference to the infected cells and host immune responses in EBV-associated diseases.
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Wang Y, Liu X, Chen Y. Adult systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease: A case report. Exp Ther Med 2015; 10:1025-1028. [PMID: 26622433 DOI: 10.3892/etm.2015.2601] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Accepted: 05/21/2015] [Indexed: 11/06/2022] Open
Abstract
Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (EBV+ T-LPD) occurs mainly in Asia and South America and is extremely rare in adults. The disease is characterized by a clonal proliferation of EBV-infected T cells with a cytotoxic immunophenotype and is associated with a poor clinical outcome and can be life-threatening. The majority of the patients have evidence of systemic disease, often with lymph node, liver and spleen involvement. The present study describes a case of adult systemic EBV+ T-LPD with high fever, systemic lymphadenopathy, hepatosplenomegaly, nose-pharynx neoplasm, pancytopenia, EB virus infection and proliferative bone marrow, with the aim of improving the understanding of the condition.
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Affiliation(s)
- Youping Wang
- Department of Oncology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Xinyue Liu
- Department of Hematology, The Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Yan Chen
- Department of Hematology, The Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
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6
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Hosoi H, Sonoki T, Murata S, Mushino T, Kuriyama K, Nishikawa A, Hanaoka N, Ohshima K, Imadome KI, Nakakuma H. Successful Immunosuppressive Therapy for Severe Infectious Mononucleosis in a Patient with Clonal Proliferation of EBV-infected CD8-positive Cells. Intern Med 2015; 54:1537-41. [PMID: 26073246 DOI: 10.2169/internalmedicine.54.3201] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 30-year-old woman was diagnosed with severe infectious mononucleosis (IM). The Epstein-Barr virus (EBV) had infected both CD19- and CD8-positive cells, and clonal proliferation of EBV-infected cells and T-cells was detected. Although we suspected malignant lymphoma, her condition improved following immunosuppressive therapy. A similar case was recently reported; therefore, this case is the second case of IM with EBV-infected CD8-positive cells and clonal proliferation of EBV-infected cells. Our results demonstrate that the clonal proliferation of EBV-infected cells is not always an indication for chemotherapy in the primary infection phase and that monitoring the EBV viral load is useful for therapeutic decision-making.
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Affiliation(s)
- Hiroki Hosoi
- Hematology/Oncology, Wakayama Medical University, Japan
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Chellapandian D, Das R, Zelley K, Wiener SJ, Zhao H, Teachey DT, Nichols KE. Treatment of Epstein Barr virus-induced haemophagocytic lymphohistiocytosis with rituximab-containing chemo-immunotherapeutic regimens. Br J Haematol 2013; 162:376-82. [PMID: 23692048 DOI: 10.1111/bjh.12386] [Citation(s) in RCA: 150] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2013] [Accepted: 03/20/2013] [Indexed: 12/13/2022]
Abstract
Haemophagocytic lymphohistiocytosis (HLH) is a life threatening complication of Epstein-Barr virus (EBV) infection. The anti-CD20 antibody rituximab depletes B cells, leading to improved outcomes for patients with EBV-associated B-lymphoproliferative disorders. To gather data on the use of rituximab in EBV-HLH, we performed a retrospective investigation involving 42 EBV-HLH patients who had received treatment with rituximab-containing regimens. On average, patients received 3 rituximab infusions (range 1-10) at a median dose of 375 mg/m(2) . In all patients, rituximab was administered with other HLH-directed medications, including steroids, etoposide and/or ciclosporin. Rituximab-containing regimens appeared well tolerated and improved clinical status in 43% of patients. Examination of laboratory data obtained prior to and within 2-4 weeks after the first rituximab dose revealed significant reductions in EBV load (median load pre-rituximab: 114,200 copies/ml, median post-rituximab: 225 copies/ml, P = 0.0001) and serum ferritin levels (median ferritin pre-rituximab: 4260 μg/l, median post-rituximab: 1149 μg/l, P = 0.001). Thus, when combined with conventional HLH-directed therapies, rituximab improves symptoms, reduces viral load and diminishes inflammation. These data support the incorporation of rituximab into future prospective clinical trials for patients with EBV-HLH.
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8
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Atypical Hydroa Vacciniforme-Like Epstein-Barr Virus Associated T/NK-Cell Lymphoproliferative Disorder. Am J Dermatopathol 2012; 34:e119-24. [DOI: 10.1097/dad.0b013e3181c036de] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
AbstractPeripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive diseases associated with poor outcome. Studies that focus specifically on PTCL are emerging, with the ultimate goal of improved understanding of disease biology and the development of more effective therapies. However, one of the difficulties in classifying and studying treatment options in clinical trials is the rarity of these subtypes. Various groups have developed lymphoma classifications over the years, including the World Health Organization, which updated its classification in 2008. This article briefly reviews the major lymphoma classification schema, highlights contributions made by the collaborative International PTCL Project, discusses prognostic issues and gene expression profiling, and outlines therapeutic approaches to PTCL. These include the standard chemotherapeutic regimens and other modalities incorporating antifolates, conjugates, histone deacetylase inhibitors, monoclonal antibodies, nucleoside analogs, proteasome inhibitors, and signaling inhibitors. As this review emphasizes, the problem has now evolved into an abundance of drugs and too few patients available to test them. Collaborative groups will aid in future efforts to find the best treatment strategies to improve the outcome for patients with PTCL.
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10
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Tai WC, Li HP, Lin TY, Lin CY, Wu MT. Response of extranodal natural killer/âT-cell lymphoma, nasal type, to interferon-α, corticosteroid and narrowband ultraviolet B phototherapy. Clin Exp Dermatol 2009; 34:e927-30. [DOI: 10.1111/j.1365-2230.2009.03714.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Wada T, Yokoyama T, Nakagawa H, Asai E, Toga A, Sakakibara Y, Shibata F, Tone Y, Shimizu M, Toma T, Yachie A. Flow cytometric analysis of skin blister fluid induced by mosquito bites in a patient with chronic active Epstein–Barr virus infection. Int J Hematol 2009; 90:611-615. [DOI: 10.1007/s12185-009-0442-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2009] [Revised: 10/13/2009] [Accepted: 10/21/2009] [Indexed: 11/29/2022]
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Chabay P, De Matteo E, Lorenzetti M, Barón AV, Valva P, Preciado MV. Low frequency of Epstein Barr virus association and high frequency of p53 overexpression in an Argentinean pediatric T-cell lymphoma series. Pediatr Dev Pathol 2009; 12:28-34. [PMID: 18540692 DOI: 10.2350/07-11-0378.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2007] [Accepted: 06/08/2008] [Indexed: 11/20/2022]
Abstract
T-cell non-Hodgkin's lymphomas (NHLs) represent 10% to 15% of all diagnosed lymphomas in Western countries. Various geographic frequencies of T-cell NHL have been documented, in part reflecting increased exposure to pathogenic factors such as Epstein-Barr virus (EBV). Our aims were to assess EBV and p53 expression in Argentine pediatric T-cell lymphoma and to correlate them with patients' survival. Epstein-Barr encoded RNAs (EBERs) in situ hybridization and LMP1 and p53 immunohistochemical staining were performed on formalin-fixed paraffin-embedded lymph node biopsies from 25 pediatric T-lymphoma patients. In 17 of 25 samples good-quality DNA was obtained, and EBER polymerase chain reaction was assessed to confirm in situ hybridization and immunohistochemical results. Epstein-Barr virus expression was found in 8.0% of cases. p53-positive staining was distributed in 92% of pediatric cases. Kaplan-Meier survival analysis showed that neither EBV nor p53 expression was statistically significantly associated with event-free survival. Our data showed a low frequency of EBV association with pediatric T-cell lymphoma. It seems that p53 plays an important role in proliferation in our studied population, since it is overexpressed in 92% of T-cell lymphoma cases.
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Affiliation(s)
- Paola Chabay
- Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina.
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13
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Epstein-Barr virus in lymphoproliferative processes: an update for the diagnostic pathologist. Adv Anat Pathol 2009; 16:40-55. [PMID: 19098466 DOI: 10.1097/pap.0b013e3181916029] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The Epstein-Barr virus is an orally transmitted herpesvirus that is widespread in human populations and exhibits marked B-cell tropism. It is associated with more human neoplasms than any other known virus, and its role in the pathogenesis of such neoplasms has been the subject of intense investigation. This review presents an overview and update of the biology of Epstein-Barr virus and the diagnostic features of lymphoproliferative disorders associated with this intriguing human pathogen.
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14
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Sato E, Ohga S, Kuroda H, Yoshiba F, Nishimura M, Nagasawa M, Inoue M, Kawa K. Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease in Japan. Am J Hematol 2008; 83:721-7. [PMID: 18626884 DOI: 10.1002/ajh.21247] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders. Its prognosis is generally poor and a treatment strategy has yet to be established. There are reports, however, that hematopoietic stem cell transplantation (HSCT) can cure this disease. To clarify the current situation regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) for EBV-associated T/NK-LPD, a nationwide survey was performed in Japan. Data for 74 patients were collected. There were 42 cases of chronic active EBV infection (CAEBV), 10 cases of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and 22 cases of EBV-associated lymphoma/leukemia (EBV-lymphoma/leukemia). Of those with CAEBV, 54% had the EBV-infected T-cell type and 59% with EBV-lymphoma/leukemia had the EBV-infected NK-cell type. Most patients with EBV-HLH and EBV-lymphoma/leukemia received allo-HSCT within 1 year after onset compared to only 14% of patients with CAEBV. The event-free survival (EFS) rate following allo-HSCT was 0.561 +/- 0.086 for CAEBV, 0.614 +/- 0.186 for EBV-HLH, and 0.309 +/- 0.107 for EBV-lymphoma/leukemia. The EFS of allo-HSCT with conventional conditioning was 0.488 +/- 0.074 and with reduced-intensity conditioning was 0.563 +/- 0.124. Thus, in a substantial number of cases, EBV-associated T/NK-LPD can be cured by either allogeneic conventional stem cell transplantation or reduced-intensity stem cell transplantation.
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MESH Headings
- Adolescent
- Adult
- Child
- Child, Preschool
- Chronic Disease
- Combined Modality Therapy
- Disease-Free Survival
- Epstein-Barr Virus Infections/complications
- Female
- Hematopoietic Stem Cell Transplantation
- Humans
- Infant
- Japan/epidemiology
- Killer Cells, Natural/pathology
- Leukemia, Large Granular Lymphocytic/epidemiology
- Leukemia, Large Granular Lymphocytic/pathology
- Leukemia, Large Granular Lymphocytic/surgery
- Leukemia, Large Granular Lymphocytic/virology
- Lymphohistiocytosis, Hemophagocytic/etiology
- Lymphoma, Non-Hodgkin/epidemiology
- Lymphoma, Non-Hodgkin/pathology
- Lymphoma, Non-Hodgkin/surgery
- Lymphoma, Non-Hodgkin/virology
- Lymphoproliferative Disorders/drug therapy
- Lymphoproliferative Disorders/epidemiology
- Lymphoproliferative Disorders/pathology
- Lymphoproliferative Disorders/surgery
- Lymphoproliferative Disorders/virology
- Male
- Middle Aged
- T-Lymphocytes/pathology
- Transplantation Conditioning
- Transplantation, Homologous
- Treatment Outcome
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Affiliation(s)
- Emiko Sato
- Department of Pediatrics, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan.
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Epstein-Barr virus persistence in the absence of conventional memory B cells: IgM+IgD+CD27+ B cells harbor the virus in X-linked lymphoproliferative disease patients. Blood 2008; 112:672-9. [DOI: 10.1182/blood-2007-10-116269] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
AbstractEpstein-Barr virus (EBV) persists in healthy virus carriers within the immunoglobulin (Ig)D−CD27+ (class-switched) memory B-cell compartment that normally arises through antigen stimulation and germinal center transit. Patients with X-linked lymphoproliferative disease (XLP) lack such class-switched memory B cells but are highly susceptible to EBV infection, often developing fatal symptoms resembling those seen in EBV-associated hemophagocytic syndrome (EBV-AHS), a disease caused by aberrant virus entry into the NK- or T-cell system. Here we show that XLP patients who survive primary EBV exposure carry relatively high virus loads in the B-cell, but not the NK- or T-cell, compartment. Interestingly, in the absence of conventional class-switched memory B cells, the circulating EBV load was concentrated within a small population of IgM+IgD+CD27+ (nonswitched) memory cells rather than within the numerically dominant naive (IgM+IgD+CD27−) or transitional (CD10+CD27−) subsets. In 2 prospectively studied patients, the circulating EBV load was stable and markers of virus polymorphism detected the same resident strain over time. These results provide the first definitive evidence that EBV can establish persistence in the B-cell system in the absence of fully functional germinal center activity and of a class-switched memory B-cell compartment.
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Aydin GB, Akyuz C, Talim B, Evans SE, Sahin S, Sari N, Tabanlioglu D, Ozen S, Cağlar M, Büyükpamukçu M. Extranodal type T/NK-cell lymphoma with an atypical clinical presentation. Pediatr Hematol Oncol 2007; 24:291-9. [PMID: 17613872 DOI: 10.1080/08880010701441112] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Peripheral-type natural killer (NK)- or T-cell lymphomas are rare disorders characterized with clonal proliferation of mature lymphocytes. They have been linked to chronic and active Epstein-Barr virus infection (CAEBV), which itself is not defined as a malignant hematological disorder. The authors present a patient with T/NK-cell lymphoma involving skin, kidneys, spleen, pancreas, and meninges. She was remarkable for having the mosaic feature of more than one type of extranodal T/NK-cell lymphoma. She also had mixed findings of CAEBV that might have been attributed both to hypersensitivity to mosquito bites and to hemophagocytic lymphohistiocytosis.
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Affiliation(s)
- G Burça Aydin
- Department of Pediatric Oncology, Hacettepe University, Institute of Oncology, Ankara, Turkey.
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Abstract
PURPOSE OF REVIEW Human natural killer cell deficiencies are a relevant clinical entity that provides insight into the role of natural killer cells in host defense, as well as the basic biology of natural killer cells. Since previously reviewing these disorders, significant developments warrant their reconsideration. RECENT FINDINGS Human natural killer cell deficiencies can occur as part of a more pervasive immunodeficiency syndrome or, rarely, in isolation. The most informative examples of the former are in the context of a known genetic defect, because the deficiency of natural killer cell development or activity can be attributed to the specific gene function. Since last reviewed, there are five human gene mutations that are now appreciated to affect natural killer cells, and additional new insights into natural killer cell biology have been obtained through seven others. Six new reports of isolated natural killer cell deficiencies, as well as a suggested classification scheme, are also reviewed. SUMMARY Appreciation of human genetic syndromes that include natural killer cell deficiencies, as well as new cases of isolated natural killer cell deficiencies, continue to advance the understanding of natural killer cell biology and solidify the role of natural killer cells in defense against human herpesviral infection.
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Affiliation(s)
- Jordan S Orange
- Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
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19
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Abstract
Epstein-Barr virus (EBV), discovered > 40 years ago from a Burkitt's lymphoma biopsy, was the first virus to be directly associated with human cancer. EBV has two distinct life cycles in the human host; a lytic form of infection that produces new infectious virions, and a latent form of infection that allows the virus to persist in a dormant state for the lifetime of the host. EBV has evolved a life cycle that mimics the natural differentiation pathway of antigen-activated B cells, giving the virus access to its site of latent infection, the resting memory B cell. By steering infected cells through the various stages of lymphocyte differentiation, EBV is able to enter a cell type suitable for long-term latent persistence and periodic reactivation. However, its presence in various stages of B-cell development, and its ability to infect certain epithelial cells, can have pathogenic consequences, and can contribute to the development of a diverse group of lymphomas and carcinomas. The presence of EBV in the tumour cells of EBV-associated cancers might provide a basis for specific therapy. This article focuses on the contributions that the virus may play in different types of human cancer, particularly Burkitt's lymphoma, Hodgkin's lymphoma, lymphomas and lymphoproliferative diseases in the immunocompromised, and nasopharyngeal and gastric carcinoma.
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Affiliation(s)
- Samuel B Pattle
- Imperial College Faculty of Medicine, Department of Virology, Norfolk Place, London, W2 1PG, UK.
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Dellon ES, Morris SR, Tang W, Dunphy CH, Russo MW. Acute liver failure due to natural killer-like T-cell leukemia/lymphoma: A case report and review of the Literature. World J Gastroenterol 2006; 12:4089-92. [PMID: 16810767 PMCID: PMC4087729 DOI: 10.3748/wjg.v12.i25.4089] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure (ALF) is a medical emergency requiring immediate evaluation for liver transplantation. We describe an unusual case of a patient who presented with ascites, jaundice, and encephalopathy and was found to have ALF due to natural killer (NK)-like T cell leukemia/lymphoma. The key immunophenotype was CD2+, CD3+, CD7+, CD56+. This diagnosis, which was based on findings in the peripheral blood and ascitic fluid, was confirmed with liver biopsy, and was a contraindication to liver transplantation. A review of the literature shows that hematologic malignancies are an uncommon cause of fulminant hepatic failure, and that NK-like T-cell leukemia/lymphoma is a relatively recently recognized entity which is characteristically CD3+ and CD56+. This case demonstrates that liver biopsy is essential in diagnosing unusual causes of acute liver failure, and that infiltration of the liver with NK-like T-cell lymphoma/leukemia can cause acute liver failure.
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Affiliation(s)
- Evan S Dellon
- University of North Carolina School of Medicine, Division of Gastroenterology and Hepatology, CB#7080, Bioinformatics Bldg, Rm 1140, 130 Mason Farm Rd, Chapel Hill, NC 27599-7080, United States.
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21
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Cho JH, Kim HS, Ko YH, Park CS. Epstein–Barr virus infected natural killer cell lymphoma in a patient with hypersensitivity to mosquito bite. J Infect 2006; 52:e173-6. [PMID: 16246422 DOI: 10.1016/j.jinf.2005.08.035] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2005] [Accepted: 08/31/2005] [Indexed: 11/24/2022]
Abstract
Hypersensitivity to mosquito bite (HMB) can occur in association with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukaemia/lymphoma, which was named 'Tokura-Ishihara disease'. This disease is very rare and most previous reports have been documented in Japan. We present a patient who suffered from of pustules on skin, high fever, myalgia and multiple lymph node enlargements after mosquito bite from childhood. Recently, multiple lymph nodes were palpable on his both inguinal area. Peripheral blood smear (PBS) revealed many large granular lymphocytes and the skin lesion showed a dense dermal and subcutaneous infiltrate of lymphocytes. The lymph nodes and perinodal adipose tissue were infiltrated by atypical lymphoid cells in which EBER-positive signals were identified by in situ hybridization using EBV encoded RNA-1 probe. He was diagnosed as having Tokura-Ishihara disease and receives chemotherapy now. Here, we report a case of this disease with a precise pathological description on the lymph node biopsy.
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Affiliation(s)
- Jae Hoon Cho
- Department of Otolaryngology, Head and Neck Surgery, Kounkuk University Medical School, Seoul, South Korea
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Woog JJ, Kim YD, Yeatts RP, Kim S, Esmaeli B, Kikkawa D, Lee HBH, Korn BS, Punja K, Habermann TM, Colgan JP, Salomao D, Cameron JD. Natural killer/T-cell lymphoma with ocular and adnexal involvement. Ophthalmology 2005; 113:140-7. [PMID: 16360212 DOI: 10.1016/j.ophtha.2005.09.036] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2005] [Revised: 09/13/2005] [Accepted: 09/29/2005] [Indexed: 10/25/2022] Open
Abstract
PURPOSE To review the clinical, radiological, and histopathologic features in 8 patients with natural killer/T-cell lymphoma (NKTL) involving the orbit and/or ocular adnexa, and to describe the responses of these patients to various treatment regimens. DESIGN Retrospective observational case series. PARTICIPANTS Eight patients (5 male, 3 female) with NKTL involving the orbit and/or ocular adnexa were identified from 1999 through 2005. The mean age at presentation was 45 years (range, 26-65). METHODS We retrospectively identified patients with NKTL of the ocular adnexa treated in the authors' medical centers from 1999 through 2004 using computerized diagnostic index retrieval. The clinical records and radiologic studies were analyzed to define modes of presentation and progression, response to therapy, and areas of anatomic involvement. Histopathologic findings, including the presence of CD3, CD56, and Epstein-Barr virus-encoded mRNA in each patient, were reviewed. MAIN OUTCOME MEASUREMENTS Time of survival from presentation to last known follow-up and tumor-related death. RESULTS Four of the 8 patients (50%) with NKTL involving the orbit or ocular adnexa had systemic involvement at presentation. Five of the 8 patients (62.5%) had concurrent sinonasal involvement, whereas 3 (37.5%) had orbital involvement alone. All lesions demonstrated CD3, CD56, and/or Epstein-Barr virus positivity on immunopathology studies. Therapy consisted of various chemotherapeutic regimens typically employed in the treatment of non-Hodgkins lymphoma, steroids, surgical intervention, and radiation. Seven (87.5%) patients died 5 weeks to 13 months after presentation, and 1 (12.5%) is alive without disease (5-year follow-up). CONCLUSIONS Natural killer/T-cell orbital lymphoma is a rare Epstein-Barr virus-associated neoplasm that may occur with or without associated sinonasal involvement. Our series, the largest cohort reported to date, demonstrates the high lethality of this condition despite aggressive conventional therapy, suggesting that new treatment options should be considered early in the course of treatment of patients with this disorder.
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Konuma T, Uchimaru K, Sekine R, Ohno N, Soda Y, Tomonari A, Ooi J, Nagamura F, Takahashi S, Iseki T, Oyaizu N, Tojo A, Asano S. Atypical Hypersensitivity to Mosquito Bites without Natural Killer Cell Proliferative Disease in an Adult Patient. Int J Hematol 2005; 82:441-4. [PMID: 16533749 DOI: 10.1532/ijh97.05019] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Hypersensitivity to mosquito bites (HMB) is a rare disorder that occurs in the first 2 decades of life and is considered to be associated with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukemia/lymphoma. EBV-encoded small nuclear RNA (EBER)-positive NK cells infiltrate the skin lesion at the site of the mosquito bite. In this report, we present the case of an adult patient with mantle cell lymphoma complicated by atypical HMB. The anti-EBV antibody titer of the patient indicated reactivation of chronic infection with this virus, and EBV DNA in the peripheral blood mononuclear cells was detected after chemotherapy by quantitative polymerase chain reaction analysis. However, an in situ hybridization analysis did not detect EBER-positive cells in the skin lesion at the bite site or in the lymph node. Peripheral NK cell lymphocytosis and EBV-associated lymphoproliferative disease did not develop. These findings suggest that some patients with chronic EBV infection may develop HMB without NK cell proliferative disease.
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Affiliation(s)
- Takaaki Konuma
- Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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Ishimura M, Ohga S, Nomura A, Toubo T, Morihana E, Saito Y, Nishio H, Ide M, Takada H, Hara T. Successful umbilical cord blood transplantation for severe chronic active Epstein-Barr virus infection after the double failure of hematopoietic stem cell transplantation. Am J Hematol 2005; 80:207-12. [PMID: 16247742 DOI: 10.1002/ajh.20430] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
An 11-year-old boy with severe chronic active Epstein-Barr virus infection (CAEBV) underwent successful cord blood transplantation (CBT) after consecutive failure of peripheral blood and bone marrow transplantation from his HLA-mismatched mother. CB cells from an unrelated donor were infused after conditioning with total body irradiation (12 Gy), melphalan (120 mg/m(2)), and etoposide (600 mg/m(2)). Complete remission without circulating EBV-DNA has continued for 15 months after a delayed hematologic recovery. This is the first successful report of CBT for CAEBV. CB may therefore be an alternate source of stem cells for the curative treatment of CAEBV, despite the absence of EBV-specific cytotoxic T lymphocytes.
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Affiliation(s)
- Masataka Ishimura
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Okano M, Kawa K, Kimura H, Yachie A, Wakiguchi H, Maeda A, Imai S, Ohga S, Kanegane H, Tsuchiya S, Morio T, Mori M, Yokota S, Imashuku S. Proposed guidelines for diagnosing chronic active Epstein-Barr virus infection. Am J Hematol 2005; 80:64-9. [PMID: 16138335 DOI: 10.1002/ajh.20398] [Citation(s) in RCA: 198] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Since the initial report of unusual manifestations possibly associated with chronic active Epstein-Barr virus (EBV) infection (CAEBV), nearly three decades have passed. During this period, reported cases with this entity have dramatically increased in the world. Additionally, recent development of diagnostic procedures, including molecular biological and immunological techniques, have provided us with the ability to define certain diseases, especially malignant disorders. Guidelines, derived mainly from the current literature and recent experiences with CAEBV in Japan, for diagnosing CAEBV are proposed to clarify this enigmatic disease.
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Affiliation(s)
- Motohiko Okano
- Department of Pediatrics, Hokkaido University Hospital, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
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26
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Satoh N, Koike T, Takato H, Fujiwara M, Emura I, Kaneganed H. Fatal Primary Epstein-Barr Virus Infection due to Clonal CD8 + T-Lymphocyte Proliferation in an Immunocompetent Adult. Int J Hematol 2005; 82:169-70. [PMID: 16146852 DOI: 10.1532/ijh97.04194] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Affiliation(s)
- Naoko Satoh
- Department of Hematology, Nagaoka Red Cross Hospital, Japan
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Lindemann TL, Greene JS. Persistent cervical lymphadenopathy in an adolescent with Epstein-Barr induced hemophagocytic syndrome: manifestations of a rare but often fatal disease. Int J Pediatr Otorhinolaryngol 2005; 69:1011-4. [PMID: 15911025 DOI: 10.1016/j.ijporl.2005.02.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2004] [Accepted: 02/05/2005] [Indexed: 11/30/2022]
Abstract
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a non-malignant proliferative disorder characterized by histiocytic proliferation and hemophagocytosis following Epstein-Barr virus infection. Though quite rare, this condition represents an often fatal disease primarily affecting the pediatric population. We discuss the case of an adolescent female who presented initially with persistent cervical lymphadenopathy and the typical findings of tonsillar hypertrophy, pharyngitis, and splenomegaly associated with infectious mononucleosis. This case study outlines the pathogenesis, common clinical findings, diagnostic criteria, and a review of the HLH-94 treatment protocol. Early recognition and treatment is emphasized because of the fulminant course of the disorder.
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Affiliation(s)
- Timothy L Lindemann
- Geisinger Medical Center, Department of Otolaryngology/Head and Neck Surgery, M.C. 13-33, 100 N. Academy Avenue, Danville, PA 17822, USA.
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Loughrey M, Trivett M, Lade S, Murray W, Turner H, Waring P. Diagnostic application of Epstein-Barr virus-encoded RNA in situ hybridisation. Pathology 2005; 36:301-8. [PMID: 15370127 DOI: 10.1080/0031302042000224584] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIMS Epstein-Barr virus (EBV) has been implicated in the pathogenesis of nasopharyngeal carcinoma and a range of proliferative lymphoid conditions. In situ hybridisation (ISH) looking for virus-encoded RNA (EBER) transcripts is performed simply using a commercially available probe. We aimed to examine the application of this test in a routine diagnostic setting. METHODS In total, 26 cases in which EBV ISH was requested for diagnostic purposes were examined. We looked at the indication for testing, the result and its implication for the final diagnosis. RESULTS Cases were classified into three categories: possible nasopharyngeal carcinoma; possible EBV-related lymphoma; and possible immunodeficiency-associated lymphoproliferative disorder. Six of nine cases of possible nasopharyngeal carcinoma were EBV ISH positive (3/3 primary and 3/6 secondary), confirming the diagnosis. Three of 14 possible lymphoma cases were EBV ISH positive which, along with appropriate ancillary tests, assisted in making the diagnoses of Burkitt's lymphoma, lymphomatoid granulomatosis and extranodal NK/T-cell lymphoma of nasal type. All of three immunodeficiency-associated cases were EBV ISH positive. Two of these were post-transplant lymphoproliferative disorders, monomorphic type. The third case was classified as HIV-related polymorphic lymphoproliferative disorder. CONCLUSIONS In our experience, EBV ISH is a straightforward and rapid procedure to perform, giving unequivocal results. Used in the appropriate clinicopathological setting it can be a highly useful ancillary diagnostic aid.
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Affiliation(s)
- Maurice Loughrey
- Department of Pathology, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria 3002, Australia.
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Li W, Wu BA, Zeng YM, Chen GC, Li XX, Chen JT, Guo YW, Li MH, Zeng Y. Epstein-Barr virus in hepatocellular carcinogenesis. World J Gastroenterol 2004; 10:3409-13. [PMID: 15526357 PMCID: PMC4576219 DOI: 10.3748/wjg.v10.i23.3409] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: In recent years, studies have suggested that Epstein-Barr virus (EBV) is associated with HCC. The present study was to determine the prevalence of EBV in HCC patients, and whether EBV acted synergistically with hepatitis viruses in HCC carcinogenesis.
METHODS: Liver tissue 115 HCC patients and 26 non-carcinoma patients were studied. Polymerase chain reaction (PCR) was performed to detect EBV BamHI W DNA, EBV LMP1 DNA, HBV X DNA, and HBV S DNA. Reverse transcription PCR (RT-PCR) was performed to detect HCV RNA and HDV RNA. Immunohistochemistry was performed to detect LMP1, HBsAg, HBcAg and HCV. The positive ratios were compared between HCC group and control group by χ2 test.
RESULTS: Totally, 78 HCC samples whose β -globulin DNA was positively detected by amplified PCR were selected. PCR was performed in all cases for EBV DNA and HBV DNA. RT-PCR was performed in 18 cases for HCV RNA and HDV RNA. EBV BamHI W and EBV LMP1 were positive in 18 and 6 cases, respectively. HBV X gene and HBV S gene were positive in 42 and 27 cases respectively. HCV was positive in one of the 18 cases, and none was positive for HDV. The positive rates were 28.2% (22 of 78) for EBV DNA (BamHI W and/or LMP1) and 56.4% (44 of 78) for HBV DNA (X gene and/or S gene) respectively. In addition, 12 cases were positive for both EBV DNA and HBV DNA. Among the 26 cases in the control group, 2 cases were positive for EBV BamHI W, 4 positive for HBV X gene and 3 positive for HBV S gene. The positive rates were 8.0% (2 of 26) and 23.1% (6 of 26), respectively, for EBV DNA and HBV DNA. The result of DNA sequencing of BamHI W was 100% homologous with the corresponding sequence of B95-8. There was significant difference in EBV infection rate between HCC patients and controls (χ2 = 4.622, P < 0.05). The difference in HBV infection rate was also significant (χ2 = 8.681, P < 0.05). However, there was no obvious correlation between HBV and EBV in HCC patients (χ2 = 0.835, P > 0.05). LMP1, HBV (HBsAg, HBcAg) and HCV were detected positively in 25, 45 and 6 of 78 cases of HCC tissues respectively. In the 26 control cases, the corresponding positive cases were 2, 4 and 0. The difference in EBV infection rate between HCC patients and control cases was statistically significant (χ2 = 6.02, P < 0.05). The difference in HBV infection rate was also statistically significant (χ2 = 10.03, P < 0.05). In the 25 cases with positive LMP1 expression, 6 were in the nuclei of tumor cells, 9 in the cytoplasm of tumor cells and 10 in mesenchymal lymphocyte cytoplasm.
CONCLUSION: The existence of EBV infection in HCC tissues suggests that EBV may be involved in the hepatocellular carcinogenesis in China. HBV infection may be a major cause of HCC. There is no correlation between EBV and HBV in the development of HCC. The prevalence of HCV infection is low in our area, and HDV appears not to play a direct role in hepatocellular carcinogenesis.
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Affiliation(s)
- Wei Li
- Department of General Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China.
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Ohga S, Nomura A, Takada H, Tanaka T, Furuno K, Takahata Y, Kinukawa N, Fukushima N, Imai S, Hara T. Dominant expression of interleukin-10 and transforming growth factor-beta genes in activated T-cells of chronic active Epstein-Barr virus infection. J Med Virol 2004; 74:449-58. [PMID: 15368517 DOI: 10.1002/jmv.20197] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Chronic active Epstein-Barr virus (EBV) infection is a chronic mononucleosis syndrome associated with clonal proliferation of EBV-carrying T-/natural killer (NK)-cells. High levels of circulating EBV and activated T-cells are sustained during the prolonged disease course, whereas it is not clear how ectopic EBV infection in T-/NK-cells has been established and maintained. To assess the biological role of activated T-cells in chronic active EBV infection (CAEBV), EBV DNA and cellular gene expressions in peripheral T-cells were quantified in CAEBV and infectious mononucleosis (IM) patients. In CAEBV, HLA-DR(+) T-cells had higher viral load and larger amounts of IFN gamma, IL-10, transforming growth factor-beta (TGF beta), and cytotoxic T lymphocyte antigen-4 (CTLA4) mRNA than HLA-DR(-)T-cells. HLA-DR(+) T cells of IM patients transcribed more IFN gamma and IL-10 than their HLA-DR(-)T cells. Expression levels of IFN gamma and forkhead box p3 (Foxp3) in CAEBV HLA-DR(+) T-cells were higher than in IM HLA-DR(+) T-cells. The effective variables to discriminate the positivity of HLA-DR were IL-10, IFN gamma, CTLA4, TGF beta, and IL-2 in the order of statistical weight. EBV load in CAEBV T-cells correlated with the expression levels of only IL-10 and TGF beta. 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. The dominant expression of regulatory cytokines in T-cells may imply a viral evasion mechanism in the disease.
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Affiliation(s)
- Shouichi Ohga
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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Abstract
PURPOSE OF REVIEW Rheumatoid arthritis is a complex multisystem disorder. The manifestations of joint disease are usually clinically apparent, but the effects of the concomitant abnormalities of immune function are more subtle. It has been suggested that patients with rheumatoid arthritis have an impaired capacity to control infection with Epstein-Barr virus. Epstein-Barr virus has oncogenic potential and is implicated in the development of some lymphomas. This review analyses the relation between Epstein-Barr virus, rheumatoid arthritis, and the risk of lymphoma and considers the effect of immunosuppression on this triad. RECENT FINDINGS Recent publications provide evidence for an altered Epstein-Barr virus-host balance in patients with rheumatoid arthritis, who have a relatively high Epstein-Barr virus load. Large epidemiologic studies confirm that lymphoma is more likely to develop in patients with rheumatoid arthritis than in the general population. The overall risk of development of lymphoma has not risen with the increased use of methotrexate or biologic agents. Histologic analysis reveals that most lymphomas in rheumatoid arthritis patients are diffuse large B cell lymphomas, a form of non-Hodgkin lymphoma. Epstein-Barr virus is detected in a proportion of these. SUMMARY Overall, patients with rheumatoid arthritis have approximately a twofold increased risk of experiencing lymphoma. Some, but not all, of this increased risk reflects an increase in Epstein-virus-associated lymphomas. This in turn may be influenced by the elevated Epstein-Barr virus load found in rheumatoid arthritis patients and may reflect subtle impairment of antiviral immunity in this group of patients.
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Affiliation(s)
- Margaret F C Callan
- Department of Immunology, Division of Medicine, Imperial College, London, UK.
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