Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease. (9/1457)

T cell immunodeficiency plays an important role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD) by permitting the unbridled expansion of Epstein-Barr virus (EBV)-infected B lymphocytes. However, factors other than T cell function may contribute to PTLD pathogenesis because PTLD infrequently develops even in the context of severe T cell immunodeficiency, and athymic mice that are T-cell-immunodeficient can reject EBV-immortalized cells. Here we report that PTLD tissues express significantly lower levels of IL-18, interferon-gamma (IFN-gamma), Mig, and RANTES compared to lymphoid tissues diagnosed with acute EBV-induced infectious mononucleosis, as assessed by semiquantitative RT-PCR analysis. Other cytokines and chemokines are expressed at similar levels. Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectious mononucleosis. IL-18, primarily a monocyte product, promotes the secretion of IFN-gamma, which stimulates Mig and RANTES expression. Both IL-18 and Mig display antitumor activity in mice involving inhibition of angiogenesis. These results document greater expression of IL-18, IFN-gamma, Mig, and RANTES in lymphoid tissues with acute EBV-induced infectious mononucleosis compared to tissues with PTLD and raise the possibility that these mediators participate in critical host responses to EBV infection.  (+info)

Polymorphism of the interleukin-10 gene is associated with susceptibility to Epstein-Barr virus infection. (10/1457)

There are indications that the cytokine interleukin (IL)-10 has a regulatory role in Epstein-Barr virus (EBV)-induced infections. Because the human IL-10 gene demonstrates polymorphism resulting in interindividual differences in cytokine production, the frequencies of the alleles defined by the base exchange polymorphism at the position -1082 (allele 1=G, allele 2=A) were analyzed in EBV-seronegative adults, seropositive adults, and in patients hospitalized because of a severe EBV infection. The frequencies of allele 1 were 0.80, 0.46, and 0.29, respectively. Because this allele is associated with a high IL-10-producing capability, these data suggest that high IL-10 levels protect against EBV infection and, conversely, that low IL-10-producing capability makes individuals more susceptible to a severe EBV infection.  (+info)

Effect of Epstein-Barr virus infection on response to chemotherapy and survival in Hodgkin's disease. (11/1457)

We have analyzed paraffin sections from 190 patients with histologically confirmed Hodgkin's disease (HD) for the presence of Epstein-Barr virus (EBV) using in situ hybridization to detect the EBV-encoded Epstein-Barr virus early RNAs (EBERs) and immunohistochemistry to identify latent membrane protein-1 (LMP1) expression. EBV was present in the tumor cells in 51 HD cases (27%) and was mainly confined to the mixed cellularity and nodular sclerosis subtypes. There was no difference between EBV-positive and EBV-negative HD patients with regard to age, clinical stage, presentation, and the number of alternating chemotherapy cycles of ChIVPP and PABIOE received. The complete remission rate after study chemotherapy was 80% in EBV-positive patients versus 69% in EBV-negative patients (P =.05). The 2-year failure-free survival rate was significantly better for EBV-positive patients when compared with the EBV-negative HD group (P =.02). Although 2-year and 5-year overall survival rates were better for EBV-positive HD patients, the differences were not statistically significant (P =.18 and P =.40, respectively). In conclusion, the results confirm the favorable prognostic value of EBV in the tumor cells of HD patients and suggest important differences in response to chemotherapy between EBV-positive and EBV-negative patients.  (+info)

Interferon gamma (IFN-gamma) deficiency in generalized Epstein-Barr virus infection with interstitial lymphoid and granulomatous pneumonia, focal cerebral lesions, and genital ulcers: remission following IFN-gamma substitution therapy. (12/1457)

A 26-year-old previously healthy woman developed granulomatous pneumonitis, encephalitis, and genital ulceration during primary Epstein-Barr virus (EBV) infection. EBV DNA was demonstrated by polymerase chain reaction analysis of serum, lung tissue, and genital ulcer specimens. Serology verified primary EBV infection. The patient lacked lymphocytes cytotoxic to autologous EBV-transformed B lymphocytes. No spontaneous or in vitro EBV-induced interferon gamma (IFN-gamma) production was evident in peripheral blood. The cells had normal IFN-gamma production when stimulated with Staphylococcus aureus exotoxin A. In the bone marrow and peripheral blood, the number of large granular CD56+ lymphocytes (natural killer cells) increased 39%-55%, but no CD4 or CD8 cell lymphocytosis was initially found. A partial clinical response was achieved with treatment with acyclovir, corticosteroids, and intravenous gamma-globulin. Because of persistent granulomatous central nervous system and lung involvement, subcutaneous IFN-gamma therapy was started but was discontinued after 3 months because of development of fever, pancytopenia, and hepatitis. This therapy initiated a complete clinical recovery, which occurred parallel to development of EBV-specific cytotoxic CD8+ T lymphocytes and normalization of natural killer cell lymphocytosis. These findings provide evidence for an EBV-induced lymphoproliferative disorder due to a T lymphocyte dysfunction associated with a selective lack of IFN-gamma synthesis.  (+info)

A new method with general diagnostic utility for the calculation of immunoglobulin G avidity. (13/1457)

The reference method for immunoglobulin G (IgG) avidity determination includes reagent-consuming serum titration. Aiming at better IgG avidity diagnostics, we applied a logistic model for the reproduction of antibody titration curves. This method was tested with well-characterized serum panels for cytomegalovirus, Epstein-Barr virus, rubella virus, parvovirus B19, and Toxoplasma gondii. This approach for IgG avidity calculation is generally applicable and attains the diagnostic performance of the reference method while being less laborious and twice as cost-effective.  (+info)

Expression of Epstein-Barr virus (EBV) transcripts encoding homologues to important human proteins in diverse EBV associated diseases. (14/1457)

AIMS: To examine the expression of Epstein-Barr virus (EBV) transcripts encoding proteins homologous to important human proteins in diverse EBV associated diseases. The proteins were: BHRF1 (homologous to Bcl-2), BDLF2 (homologous to cyclin B1), BARF1 (homologous to intercellular cell adhesion molecule 1 (ICAM-1)), and BCRF1 (viral IL-10 (vIL-10), homologous to human IL-10 (hIL-10)). METHODS: Six cases of oral hairy leukoplakia, seven of Hodgkin's disease, eight of T cell non-Hodgkin's lymphoma, and nine of nasopharyngeal carcinoma were examined at the mRNA level using either the reverse transcriptase polymerase chain reaction (RT-PCR) or nucleic acid sequence based amplification (NASBA). Different primer sets allowed the differentiation by RT-PCR of the latent (Cp/Wp driven) and lytic (Hp driven) transcripts of BHRF1. A specific NASBA reaction was developed for the detection of vIL-10 and BDLF2 transcripts and this was tested initially on cell lines and later on clinical samples. RESULTS: vIL-10 and BDLF2 were expressed almost exclusively in oral hairy leukoplakia, whereas BARF1 transcripts were present in all cases of nasopharyngeal carcinoma, with weak expression in one oral hairy leukoplakia and isolated cases of lymphoid malignancy. Both BHRF1 transcripts were detected across the range of tissues tested, but strong expression of lytic BHRF1 transcripts was seen only in oral hairy leukoplakia. CONCLUSIONS: vIL-10 and BDLF2 transcripts are expressed during productive EBV infection and are unlikely to be important in the pathogenesis of EBV associated malignancies. BARF1 appears to be expressed preferentially during viral latency and is more closely associated with malignant rather than benign epithelial proliferations. The alternative transcripts derived from the BHRF1 open reading frame may have very different roles during latent or productive infection.  (+info)

Increased incidence of Hodgkin's disease after allogeneic bone marrow transplantation. (15/1457)

PURPOSE: Immune dysregulation associated with allogeneic bone marrow transplantation (BMT) is linked to an increased risk of posttransplant lymphoproliferative disorders (PTLD); however, reports of Hodgkin's disease (HD) after transplantation are rare. PATIENTS AND METHODS: We evaluated the risk of HD among 18,531 persons receiving allogeneic BMT between 1964 and 1992 at 235 centers. The number of HD cases was compared with that expected in the general population. Risk factors were identified using Poisson regression and a nested case-control study. RESULTS: Risk of HD was increased in the postBMT population compared with the general population with an observed-to-expected incidence ratio (O/E) of 6.2 (observed cases, n = 8; 95% confidence interval [CI], 2.7 to 12). A significantly increased risk of HD remained after excluding two human immunodeficiency virus-positive patients (observed cases, n = 6; O/E = 4.7, 95% CI, 1.7 to 10.3). Mixed cellularity subtype predominated (five of eight cases, 63%). Five of six assessable cases contained Epstein-Barr virus (EBV) genome. Posttransplant HD differed from PTLD by later onset (> 2.5 years) and lack of association with established risk factors (such as T-cell depletion and HLA disparity). Patients with HD were more likely than matched controls to have had grade 2 to 4 acute graft-versus-host disease (GVHD), required therapy for chronic GVHD, or both (P =.002), although analysis included small numbers of patients. CONCLUSION: The increased incidence of HD among BMT recipients adds support to current theories which link overstimulation of cell-mediated immunity and exposure to EBV with various subtypes of HD. The long latency of HD after transplant and lack of association with risk factors for PTLD is noteworthy and should be explored further for possible insights into pathogenesis.  (+info)

B cell non-Hodgkin's lymphoma in a girl with the DiGeorge anomaly. (16/1457)

The DiGeorge anomaly (DGA) is occasionally associated with cellular immunodeficiency. We report a female infant diagnosed with complete DGA, who developed fatal, high grade, non-Hodgkin's lymphoma that expressed Epstein-Barr virus (EBV). Non-Hodgkin's lymphoma should be considered in children with DGA.  (+info)