-
The Journal of pediatrics 04/2013; · 4.02 Impact Factor
-
Masaki Fukuda,
Ryosei Nishimura,
Raita Araki,
Rie Kuroda,
Shintaro Mase,
Yasuhiro Nakagawa,
Yumi Tone,
Hideaki Maeba,
Taizo Wada, Yoshihito Kasahara,
Akihiro Yachie
[show abstract]
[hide abstract]
ABSTRACT: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is characterized by clonal expansion of EBV-infected CD8(+)T-cells. We have recently demonstrated that detection of a clonally expanded population of EBV-infected CD8(+)T-cells with CD5 down-regulation was a useful tool to distinguish EBV-HLH from EBV-related disorders such as severe infectious mononucleosis. A 5-year-old girl who presented with fever, pancytopenia and liver dysfunction was diagnosed by this method in addition to conventional diagnostic tests. Further, EBV-infected cells were identified as CD5(-)HLA-DR(+) TCR V β3(+) CD8(+)T cells, an increase or decrease of which over time reflected the disease severity in this patient. Treatment of patients with EBV-HLH varies from steroid alone to intensive chemotherapy or hematopoietic stem cell transplantation. Easy monitoring of EBV-infected cells by using flow cytometry over time may provide useful information to choose an appropriate treatment for each individual patient with EBV-HLH.
[Rinshō ketsueki] The Japanese journal of clinical hematology 03/2012; 53(3):337-41.
-
[show abstract]
[hide abstract]
ABSTRACT: Chronic active Epstein-Barr virus infection (CAEBV) is defined as a systemic EBV-associated lymphoproliferative disease characterized by fever, lymphadenopathy, and splenomegaly in apparently immunocompetent persons. Recent studies have revealed that EBV infects T or natural killer cells in most patients with CAEBV; the etiology of CAEBV, however, remains unknown. Autoimmune lymphoproliferative disorder (ALPS) is an inherited disorder associated with defects in apoptosis, and clinically characterized by lymphadenopathy, splenomegaly, hypergammaglobulinemia, and autoimmune disease. ALPS is most often associated with mutations in the FAS gene, which is an apoptosis-signaling receptor important for homeostasis of the immune system. Based on the clinical similarity between ALPS and CAEBV with respect to lymphoproliferation, we have examined the possibility of the co-occurrence of ALPS in patients with a diagnosis of CAEBV. In this study, we have identified FAS gene mutations in three Japanese patients with lymphadenopathy, hepatosplenomegaly, and unusual EBV infection, who were diagnosed with CAEBV. These observations, which indicate that the clinical development of ALPS may be associated with EBV infection, alert us to a potential diagnostic pitfall of CAEBV.
International journal of hematology 06/2011; 93(6):760-4. · 1.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To compare the pro-inflammatory cytokine profiles and the cytokine kinetics in patients with secondary macrophage activation syndrome (MAS) due to systemic-onset juvenile idiopathic arthritis (s-JIA) and in both active and inactive disease states of s-JIA (but no MAS), with those demonstrated in EBV-induced haemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD), and to investigate the significance of IL-18 in the pathogenesis of s-JIA.
Five patients with MAS complicating s-JIA (MAS/s-JIA), 10 with HLH due to EBV infection (EBV-HLH), 22 with KD and 28 healthy controls were analysed. Cytokine concentrations (IL-18, IL-6, neopterin and TNF-alpha receptor Types I and II) were quantified in serum by ELISA. Results were compared with clinical features of MAS/s-JIA, including ferritin concentrations.
Serum IL-18 concentrations in MAS/s-JIA patients were significantly higher than those in EBV-HLH or KD patients (P < 0.05). Serum IL-6 concentrations in KD patients were significantly higher than those in EBV-HLH or MAS/s-JIA patients. Serum neopterin concentrations in EBV-HLH patients were significantly higher than those in MAS/s-JIA or KD patients. Serum IL-18 correlated positively with the following measurements of disease activity: CRP, ferritin, lactate dehydrogenase and other cytokines (P < 0.05). Serum concentrations of IL-18 in s-JIA patients remained elevated in the inactive phase of disease, whereas clinical parameters and other cytokines normalized.
IL-18 may be an important mediator in s-JIA. Although serum Il-18 concentrations correlated with markers of the disease activity, IL-18 concentrations remained elevated even when other markers of disease activity normalized. Serum IL-18 concentration may be a promising indicator of the disease activity. The cytokine release pattern in MAS/HLH is different among patients with different aetiologies. Monitoring the cytokine profile, including IL-18, may be useful for differentiation of MAS/HLH and evaluation of disease activity in s-JIA.
Rheumatology (Oxford, England) 09/2010; 49(9):1645-53. · 4.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chronic active Epstein-Barr virus infection (CAEBV) is a unique and fatal lymphoproliferative disease (LPD), which often shows high serum IgG and/or IgE. The significance of such immunoglobulin abnormalities in CAEBV has not been fully evaluated and discussed. In addition, such clinical features mimic HIV-1 infection. We report here a case of CAEBV with M-protein detected which may shed a new light on the pathogenesis of this disease.
International journal of hematology 08/2009; 90(2):235-8. · 1.17 Impact Factor
-
Taizo Wada,
Masahiro Yasui,
Tomoko Toma,
Yuko Nakayama,
Mika Nishida,
Masaki Shimizu,
Michiko Okajima, Yoshihito Kasahara,
Shoichi Koizumi,
Masami Inoue,
Keisei Kawa,
Akihiro Yachie
[show abstract]
[hide abstract]
ABSTRACT: X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain (gammac) and usually characterized by the absence of T and natural killer (NK) cells. Here, we report an atypical case of XSCID presenting with autologous T and NK cells and Omenn syndrome-like manifestations. The patient carried a splice-site mutation (IVS1+5G>A) that caused most of the mRNA to be incorrectly spliced but produced normally spliced transcript in lesser amount, leading to residual gammac expression and development of T and NK cells. The skin biopsy specimen showed massive infiltration of revertant T cells. Those T cells were found to have a second-site mutation and result in complete restoration of correct splicing. These findings suggest that the clinical spectrum of XSCID is quite broad and includes atypical cases mimicking Omenn syndrome, and highlight the importance of revertant mosaicism as a possible cause for variable phenotypic expression.
Blood 07/2008; 112(5):1872-5. · 9.90 Impact Factor
-
Fumie Shibata,
Tomoko Toma,
Taizo Wada,
Masayuki Inoue,
Yumi Tone,
Kazuhide Ohta, Yoshihito Kasahara,
Fumie Sano,
Mitsuaki Kimura,
Mitsuru Ikeno,
Shoichi Koizumi,
Akihiro Yachie
[show abstract]
[hide abstract]
ABSTRACT: We observed a patient with X-linked severe combined immunodeficiency (X-SCID) with Omenn syndrome-like manifestations. X-linked inheritance, absence of CD132 expression and impaired response to interleukin-2 (IL-2) indicated that the case is typical of X-SCID due to gamma(c) defect. However, this case was unusual in that circulating natural killer (NK) cells were increased and nearly half of these NK cells exhibited the CD56(bright) CD16(-) phenotype. A missense mutation was found within exon 5 of the IL2RG gene. The identical mutation was detected within NK, CD4(+) T and B cells. Engraftment of maternally derived NK cells or gene reversion was ruled out. The erythroderma-like skin lesion was characterized by infiltration of the dermis by CD56(bright) NK cells admixed with CD1a(+) dendritic cells (DC). Expression of mRNA for inflammatory cytokines was significantly enhanced within the skin. This may be the first human case to demonstrate that close cell-to-cell contact between DC and NK cells provides an effective alternative pathway for NK cell differentiation/activation in vivo.
European Journal Of Haematology 08/2007; 79(1):81-5. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder caused by mutations in the ITGB2 (CD18) gene and characterized by recurrent severe infections, impaired pus formation, and defective wound healing. We describe an unusual case of severe phenotypic LAD-1 presenting with somatic mosaicism. The patient is a compound heterozygote bearing 2 different frameshift mutations that abrogate protein expression. However, CD18 expression was detected in a small proportion of T cells but was undetectable in granulocytes, monocytes, B cells, and natural killer (NK) cells. The T cells were not of maternal origin, lacked the paternal mutation, and showed a selective advantage in vivo. Molecular analysis using sorted CD18+ cells revealed them to be derived from a single CD8+ T cell carrying T-cell receptor VB22. These findings suggest that spontaneous in vivo reversion was responsible for the somatic mosaicism in our patient.
Blood 03/2007; 109(3):1182-4. · 9.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Type 1 diabetes mellitus (type 1 DM) is the disease of insulin deficiency due to the destruction of islet cells of the pancreas, presumably through the pathogenic process mediated by autoreactive T cells. In many autoimmune diseases, oligoclonal expansion of autoreactive T cells have been reported recently. It is also suggested that proliferation of T cell clones which recognize pancreatic beta cell antigen are involved in the pathogenesis of type 1 DM. In this study, the diversity of T cell receptor (TCR) structures were evaluated in patients with type 1 DM by analyzing TCR Vbeta repertoire and complementarity determining region 3 (CDR3) size distributions of circulating T cells. Increase of specific TCR Vbeta repertoires was often observed in patients with positive anti-glutamic acid decarboxylase antibody, and this tendency was more evident among CD8+ T cells than in CD4+ T cells. Reductions of CDR3 sizes were frequently seen among CD8+ T cells from patients whose onset was within 10 years. These results suggested that selective expansion of CD8+ T cell clones play roles in the pathogenesis of type 1 DM.
Rinsho byori. The Japanese journal of clinical pathology 02/2007; 55(2):112-9.
-
Kazuhide Ohta,
Masaki Shimizu,
Akiko Nakai,
Tomoko Toma, Yoshihito Kasahara,
Chihiro Arii,
Akihiro Yachie,
Takeshi Kawamura,
Atsushi Aikawa,
Akira Hasegawa,
Kazutaka Sato,
Hitoshi Yokoyama,
Isao Ishikawa,
Shoichi Koizumi
[show abstract]
[hide abstract]
ABSTRACT: A patient who underwent living donor kidney transplantation was infected with Epstein-Barr virus (EBV) that resulted in persistent EBV infection and EBV-associated chronic hepatitis, determined by abnormally elevated anti-EBV antibody titers and high frequency of EBV-infected B lymphocytes. Despite decreases in immunosuppressant doses, persistent EBV infection and chronic hepatitis persisted for several years. Therapy using anti-CD20 monoclonal antibody (rituximab) virtually eliminated peripheral B lymphocytes and EBV-encoded small RNA 1 (EBER-1)-positive cells. Moreover, hepatic enzyme levels normalized and histological findings indicated marked improvement in hepatic inflammation. Although peripheral CD20(+) B lymphocyte and EBER-1-positive cell levels began to increase 4 months after the end of therapy, the number of EBER-1-positive cells remained very low, and liver function test results remained within normal ranges. The present case illustrates the significance of early diagnosis, monitoring of viral load, and vigorous management of EBV-related disorders associated with organ transplantation.
American Journal of Kidney Diseases 01/2007; 48(6):986-9. · 5.43 Impact Factor
-
Masaki Shimizu,
Kazuhide Ohta,
Yonghong Yang,
Akiko Nakai,
Tomoko Toma,
Yutaka Saikawa, Yoshihito Kasahara,
Akihiro Yachie,
Hitoshi Yokoyama,
Hidetoshi Seki,
Shoichi Koizumi
[show abstract]
[hide abstract]
ABSTRACT: To clarify the patterns of heme oxygenase-1 (HO-1) production within the human kidney, we examined HO-1 mRNA expression in various renal diseases and compared the patterns with those of HO-1 protein expression and these data with the clinical features. The degrees of hematuria and proteinuria and the levels of urinary N-acetyl-beta-D-glucosaminidase (NAG), beta(2)-microglobulin (beta(2)-mg), and creatinine were determined. In situ hybridization and immunohistochemical studies were performed to evaluate HO-1 expression. HO-1 mRNA was detectable within tubular, glomerular, and Bowman's epithelial cells and infiltrating macrophages. Within the proximal tubuli, there was a correlation between expression of HO-1 protein and mRNA, but the intensity of HO-1 mRNA expression was much less than expected from the levels of protein. In contrast, both HO-1 protein and mRNA were expressed at significant levels within distal tubuli. Furthermore, there was no correlation with both expressions within distal tubuli. HO-1 mRNA expression within tubular, glomerular, and Bowman's epithelial cells tended to be more intense with greater degrees of proteinuria. However, there was little correlation between the intensity of HO-1 mRNA expression and the degree of hematuria, NAG, and beta(2)-mg. HO-1 plays important roles in maintaining renal functions by protecting renal epithelial cells from glomerular proteinuria, which can become a cause of oxidative stress. Furthermore, from the different expression pattern of HO-1 gene between within the proximal tubuli and within the distal tubuli, renal expression of HO-1 is regulated in a segment-specific manner, with HO-1 thereby playing distinct roles in different segments of the nephron to maintain renal functions.
Pediatric Research 11/2005; 58(4):666-71. · 2.70 Impact Factor
-
Taizo Wada,
Tomoko Toma,
Hiroyuki Okamoto, Yoshihito Kasahara,
Shoichi Koizumi,
Kazunaga Agematsu,
Hirokazu Kimura,
Akira Shimada,
Yasuhide Hayashi,
Masahiko Kato,
Akihiro Yachie
[show abstract]
[hide abstract]
ABSTRACT: Omenn syndrome (OS) is a rare primary immunodeficiency characterized by the presence of activated/oligoclonal T cells, eosinophilia, and the absence of circulating B cells. OS patients carry leaky mutations of recombination activating genes (RAG1 or RAG2) resulting in partial V(D)J recombination activity, whereas null mutations cause severe combined immunodeficiency with absence of mature T and B cells (T-B- SCID). Here we describe somatic mosaicism due to multiple second-site mutations in a patient with RAG1 deficiency. We found that he is homozygous for a single base deletion in the RAG1 gene, which results in frameshift and likely abrogates the protein function. However, the patient showed typical OS features. Molecular analysis revealed that several second-site mutations, all of which restored the RAG1 reading frame and resulted in missense mutations, were demonstrated in his T cells. These findings suggest that his revertant T-cell mosaicism is responsible for OS phenotype switched from T-B- SCID.
Blood 10/2005; 106(6):2099-101. · 9.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We compared the amount of serum Epstein-Barr virus DNA (EBV-DNA) detected in patients with nasopharyngeal carcinoma (NPC) in a high-incidence area, represented by Taiwan, and a low-incidence area, represented by Japan, using real-time quantitative PCR. The median serum EBV-DNA value in 41 Japanese NPC cases was 5450 copies/ml, and that in in 23 Taiwanese cases was 2125 copies/ml. The median serum EBV-DNA value in all 64 NPC cases was significantly higher than in control groups. Using receiver-operating-characteristic (ROC) curves, the sensitivity and specificity of EBV-DNA quantification were determined (cut-off point, 6.87 copies/ml; sensitivity, 0.855; specificity, 0.885) and compared with those of EBV-viral-capsid-antigen (VCA) titers; the results showed that EBV-DNA was a more sensitive and specific parameter than EBV-VCA titer. Then, we analyzed 19 NPC patients in whom recurrence developed (11 Japanese and 8 Taiwanese), and 26 NPC patients in continuous remission. Although there was no significant difference in EBV-DNA values between Japanese and Taiwanese patients, the value was significantly higher in the 19 patients with recurrence than in those in remission. ROC analysis again revealed a higher diagnostic value of EBV-DNA than EBV-VCA. These results suggest EBV-DNA is a more reliable tumor marker than EBV-VCA in both high-incidence and low-incidence areas of NPC.
Cancer Science 08/2005; 95(6):508 - 513. · 3.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Dyskeratosis congenita (DC) is a rare inherited multisystem disorder characterized by the triad of abnormal skin pigmentation, nail dystrophy and mucosal leucoplakia. X-linked recessive inheritances are recognized in approximately 40% of the patients. DKC1 has been identified as the gene responsible for X-linked DC, and genetic analyses have been performed in a worldwide study. Here, we performed genetic analysis of five Japanese patients with presumed X-linked DC, and identified four mutations in the DKC1 gene, including two novel missense mutations (Q31K and T357A). Such genetic analysis is useful for the definite diagnosis and genetic counselling of patients.
British Journal of Haematology 06/2005; 129(3):432-4. · 4.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There has been increasing evidence suggesting the potent anti-inflammatory roles of heme oxygenase-1 (HO-1) in protecting renal tubular epithelial cells, vascular endothelial cells, and circulating monocytes. Based on these findings, novel therapeutic interventions have been proposed to control the expression of endothelial HO-1 levels to ameliorate various vascular diseases. We evaluated the effect of HO-1 gene transfer into an anchorage-dependent cell, ECV304. Effect of HO-1 production on the cell injury induced by hydrogen peroxide was evaluated after hemin stimulation and after HO-1 gene transfection. Morphological changes and the induction of various anti-apoptotic proteins were examined at the same time. Levels of HO-1 expression were variable in different clones of HO-1-transfected ECV304 cells. Among these, the clones with moderate levels of HO-1 expression were significantly more resistant to oxidative stress. In contrast, those with the highest levels of HO-1 exhibited paradoxically enhanced susceptibility to oxidative injury. Interestingly, the cell survival after oxidative stress was in parallel with the levels of Bcl-2 expression and of fibronectin receptor, alpha5 integrin. It is suggested from these results, that excessive HO-1 not only leads to enhanced cell injury, but also prolongs the repair process of the injured endothelial tissue. However, HO-1 reduces the oxidative cell injury and protects the endothelial cells, if its expression is appropriately controlled.
Journal of Cellular Biochemistry 11/2004; 93(3):552-62. · 2.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We compared the amount of serum Epstein-Barr virus DNA (EBV-DNA) detected in patients with nasopharyngeal carcinoma (NPC) in a high-incidence area, represented by Taiwan, and a low-incidence area, represented by Japan, using real-time quantitative PCR. The median serum EBV-DNA value in 41 Japanese NPC cases was 5450 copies/ml, and that in in 23 Taiwanese cases was 2125 copies/ml. The median serum EBV-DNA value in all 64 NPC cases was significantly higher than in control groups. Using receiver-operating-characteristic (ROC) curves, the sensitivity and specificity of EBV-DNA quantification were determined (cut-off point, 6.87 copies/ml; sensitivity, 0.855; specificity, 0.885) and compared with those of EBV-viral-capsid-antigen (VCA) titers; the results showed that EBV-DNA was a more sensitive and specific parameter than EBV-VCA titer. Then, we analyzed 19 NPC patients in whom recurrence developed (11 Japanese and 8 Taiwanese), and 26 NPC patients in continuous remission. Although there was no significant difference in EBV-DNA values between Japanese and Taiwanese patients, the value was significantly higher in the 19 patients with recurrence than in those in remission. ROC analysis again revealed a higher diagnostic value of EBV-DNA than EBV-VCA. These results suggest EBV-DNA is a more reliable tumor marker than EBV-VCA in both high-incidence and low-incidence areas of NPC.
Cancer Science 07/2004; 95(6):508-13. · 3.33 Impact Factor
-
Yonghong Yang,
Kazuhide Ohta,
Masaki Shimizu,
Kayoko Morimoto,
Chinami Goto,
Akiko Nakai,
Tomoko Toma, Yoshihito Kasahara,
Akihiro Yachie,
Hidetoshi Seki,
Shoichi Koizumi
[show abstract]
[hide abstract]
ABSTRACT: The renal pathology of human heme oxygenase (HO)-1 deficiency is characterized by advanced tubulointerstitial injury, whereas the glomerular structures are affected little. These facts suggest that the renal tubuli are dependent on intrinsic HO-1 production for their survival under oxidative stresses.
We compared the patterns of HO-1 expression by primary cultured human mesangial cells (HMCs) and renal proximal tubular epithelial cells (HRPTECs) in vitro. Furthermore, the cytoprotective roles of HO-1 induced in these cells were evaluated by stress-induced cytotoxicity assays. HO-1 expressions in HRPTECs and HMCs were evaluated by immunoblotting, and by reverse transcriptase (RT) and/or real time polymerase chain reaction (PCR).
In HRPTECs, both HO-1 mRNA expression and protein production peaked at around 12 h and persisted until 24 h after hemin stimulation. In contrast, HO-1 mRNA expression and protein production by HMCs peaked at 4 h and 6 h respectively, and the levels declined rapidly, being undetectable at 24 h. The peak level of HO-1 expression was significantly higher in HRPTECs than in HMCs. Oxidative stress-induced cell injury in HRPTECs was significantly reduced when HO-1 production had been induced prior to the culture. In contrast, HO-1 induction had little cytoprotective effect on HMCs. Tin protoporphyrin (SnPP), an inhibitor of HO function, significantly reversed the cytoprotection by HO-1.
These data suggest that HRPTECs are more susceptible to oxidative stress and are significantly more dependent on HO-1 for protection against noxious stimuli than HMCs. Collectively, these results indicate that HO-1 is an important protective factor for kidney tissue, in particular, renal tubular epithelial cells.
Kidney International 11/2003; 64(4):1302-9. · 6.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Monocytes play key roles both in innate and adaptive antigen-specific immunity and they constitute critical components of the immune responses. Although most of the monocyte-derived cytokines exhibit proinflammatory functions in vivo, heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, exerts potent anti-inflammatory effect through production of carbon monoxide and bilirubin. We compared HO-1 production by monocytes in vivo in various acute inflammatory illnesses and in normal controls. Freshly isolated monocytes produced little HO-1 as detected by immunohistochemistry, but it was rapidly induced in vitro upon stimulation. HO-1 production by monocytes was selective because it was not induced in other leukocyte populations, including granulocytes and lymphocytes. Monocytes from acute inflammatory illnesses, such as Kawasaki disease and acute infectious diseases, viral or bacterial, produced significant levels of HO-1, as detected by flow cytometry, immunohistochemistry, and reverse transcription polymerase chain reaction. Quantitative analysis of HO-1 mRNA expression by real-time polymerase chain reaction revealed that monocytes from controls exhibited low, but significant levels of HO-1 mRNA, indicating that circulating monocytes produce HO-1 constantly, in response to basal level of oxidative stress encountered daily. Significantly elevated HO-1 mRNA levels seen in acute inflammatory illnesses suggest that monocyte HO-1 production serve as potent anti-inflammatory agent to control excessive cell or tissue injury in the presence of oxidative stress and cytokinemia.
Experimental Biology and Medicine 06/2003; 228(5):550-6. · 2.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Epstein-Barr virus (EBV) is a ubiquitous virus that infects the majority of the world population by adulthood. The major target for infection is the B lymphocyte, and acute infection causes vigorous EBV-specific killer T-cell responses exemplified clinically by acute infectious mononucleosis (IM). EBV infection usually persists latently life-long without eliciting any clinical symptoms. Rarely, active EBV infection is prolonged, with abnormal expansions of EBV-infected T or NK cells, conditions collectively defined here as EBV-associated T/NK lymphoproliferative diseases. Hemophagocytic lymphohistiocytosis (HLH), chronic active EBV infection (CAEBV), NK lymphoma/leukemia, and T-cell lymphoma are entities included in this category. Hypersensitivity to mosquito bite (HMB) represents a unique syndrome characterized by expansion of EBV-infected NK cells in the peripheral circulation and within the inflammatory skin lesions induced by mosquito bites. Target cell specificity, defects in host immune responses, and strain differences of EBV may account for ectopic EBV infections and for the unique clinical presentations characteristic of each illness.
Seminars in Hematology 05/2003; 40(2):124-32. · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: While Epstein-Barr virus (EBV) tropism in B cells and nasopharygeal epithelial cells in the normal host has been demonstrated, recently the role of its infection into non-B cell populations has been suggested to play a pivotal role in the pathogenesis of several EBV-related hematological as well as non-hematological diseases. Ectopic EBV infection in T cells or natural killer (NK) cells has been reported in EBV-associated hematological diseases, such as acute fulminant EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). Recent advances in the analysis of EBV infection in lymphocyte subpopulations have clarified the differential virus-cell interaction within these EBV-related disorders. EBV infection was predominantly found in CD8(+) T-cells from EBV-HLH, and in CD4(+) T-cells or NK cells from CAEBV, while the majority of EBV infected cells were found in B cells from acute infectious mononucleosis (IM). Different virus-cell interactions between acute EBV-HLH and CAEBV have indicated different pathogenic mechanisms against EBV infection between the two EBV-associated diseases, accounting for the difference in clinical manifestations between the two diseases.
Critical Reviews in Oncology/Hematology 01/2003; 44(3):283-94. · 4.41 Impact Factor
