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At least 1,225 records · Page 68Linked to original sources
PubMed1997

Immunohistochemical detection of the Epstein-Barr virus-encoded latent membrane protein 2A in Hodgkin's disease and infectious mononucleosis.

We describe two new monoclonal antibodies specific for the Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) that are suitable for the immunohistochemical analysis of routinely processed paraffin sections. These antibodies were applied to the immunohistochemical detection of LMP2A in Hodgkin's disease (HD). LMP2A-specific membrane staining was seen in the Hodgkin and Reed-Sternberg (HRS) cells of 22 of 42 (52%) EBV-positive HD cases, but not in 39 EBV-negative HD cases. In lymphoid tissues from patients with acute infectious mononucleosis (IM), interfollicular immunoblasts were shown to express LMP2A. This is the first demonstration of LMP2A protein expression at the single-cell level in EBV-associated lymphoproliferations in vivo. The detection of LMP2A protein expression in HD and IM is of importance in view of the proposed role of this protein for maintaining latent EBV infection and its possible contribution for EBV-associated transformation. Because LMP2A provides target epitopes for EBV-specific cytotoxic T cells, the expression of this protein in HRS cells has implications for the immunotherapeutic approaches to the treatment of HD.

Animals↗
PubMed2000

[Fatal infectious mononucleosis during azathioprine treatment in Crohn's disease].

The benefits of immunosuppressive agents in inflammatory bowel disease have been the subject of controversy. However, extensive clinical data have conclusively proved their efficacy with respect to potential toxicity. Azathioprine is one of the most widely used immunosuppressive agents in the treatment of Crohn's disease and its effectiveness has been proved in corticosteroid dependent, corticosteroid-refractory and fistulizing Crohn's disease. We present a 24-year-old male, treated with azathioprine for corticosteroid dependent Crohn's disease who was admitted to hospital with constant fever, lymphadenopathy and liver function abnormalities secondary to infectious mononucleosis after a primary infection with Epstein-Barr virus. The patient developed constitutional symptoms and progressive jaundice and 14 days after hospital admission died because of massive upper gastrointestinal bleeding due to hemorrhagic erosive gastropathy.

Adult↗
PubMed1980

Long-term T-cell-mediated immunity to Epstein-Barr virus in man. IV. Development of T-cell memory in convalescent infectious mononucleosis patients.

Under appropriate culture conditions, EB virus infection of lymphocytes from seropositive donors leads to regression of transformation, and this was shown previously to be due to activation in a secondary immune response to T lymphocytes inhibitory for the autologous lymphoblastoid cell line. Regression can be quantified by determining the number of cells required for its expression. To investigate the development of memory T cells with EB-virus specificity in the primary infection, a comparison was made of the capacity for regression of lymphocytes from 16 cases of infectious mononucleosis (IM) and 13 normal donors. With 9 normal seropositive donors a mean lymphocyte concentration of 4.6 X 10(5)/ml was required to achieve 50% regression. In contrast, with 8 cases of IM tested within 1 week of onset, a much higher mean lymphocyte concentration (3.7 X 10(6)/ml) was necessary. Six of these IM cases, and another not tested in the first week, were tested on several occasions between 5 and 23 weeks after onset, and showed a slight reduction in the mean cell concentration required for regression (1.5 X 10(6)/ml). Six additional were tested 23--83 weeks after onset by which time the cell concentration required for 50% regression (mean = 4.5 X 10(5)/ml) had reached the level shown by normal seropositive donors. Regression did not occur with lymphocytes from seronegative donors, even at the highest cell concentration. Recombination cultures of T-cell-depleted and T-cell-enriched lymphocyte populations from 3 IM cases in ratios of 1:7 to 7:1 showed that the failure of regression in acute IM was not due simply to lack of sufficient numbers of T cells. The results indicate that EB-virus-specific memory T-cell activity as detected by the regression test is absent in the acute phase of IM, becomes evident at low levels 5--23 weeks after onset, and reaches a maximum after about 6 months.

Acute Disease↗
PubMed1979

Induction of plaque-forming cells in human blood lymphocytes cultured in the presence of antigen and Epstein-Barr virus: a study with normal donors and infectious mononucleosis patients.

Normal human peripheral blood lymphocytes, stimulated in vitro with SRBC in the presence of Epstein-Barr virus (EBV), gave rise to plaque-forming cells (PFC) specific for the antigen. PFC levels were very low before day 4 and increased thereafter, reaching a maximum around day 8. However, the kinetics of the response varied considerably from donor to donor and from experiment to experiment. In some instances a second peak of PFC was obtained beyond day 10. Large differences in the magnitude of the response were observed among different normal donors, the overall responsiveness range covering four orders of magnitude. Peripheral blood lymphocytes from infectious mononucleosis patients in the acute stage of the disease, when a high titre of heterophil and anti-EBV antibodies were present, did not give rise to PFC. A return to normal responses was observed during recovery from the disease.

Adult↗
PubMedDate not supplied

The ocular manifestations of herpes zoster, varicella, infectious mononucleosis, and cytomegalovirus disease.

Herpes zoster, caused by varicella-zoster (V-Z) virus which also causes varicella (chickenpox), is usually a benign self-limited disease. However, when the ophthalmic division of the trigeminal nerve is affected, the ocular disease (ophthalmic zoster), although also usually mild and self-limited, may have severe complications (corneal scarring, glaucoma, iris atrophy, posterior synechiae, scleritis, motor disturbances, optic neuritis, retinitis, anterior segment necrosis, and phthisis bulbi and servere postherpetic neuralgia). Varicella affects the eye rarely (except for the typical lid lesions), but associated conjunctival and corneal lesions, iridocyclitis, glaucoma, chorioretinitis, and optic nerve lesions have been described. Infectious mononucleosis may involve the eye either by direct involvement or from a remote focus such as the central nervous system. Ocular manifestations of cytomegalovirus disease is usually limited to the choroid and retina unless involvement of the developing embryo occurs prior to the development of the eye.

Adolescent↗
PubMed1996

Development of Epstein-Barr virus-specific memory T cell receptor clonotypes in acute infectious mononucleosis.

The importance of cytotoxic T lymphocytes (CTLs) in the immunosurveillance of Epstein-Barr virus (EBV)-infected B cells is firmly established, and the viral antigens of CTL recognition in latent infection are well defined. The epitopes targeted by CTLs during primary infection have not been identified, however, and there is only limited information about T cell receptor (TCR) selection. In the present report, we have monitored the development of memory TCR-beta clonotypes selected in response to natural EBV infection in a longitudinal study of an HLA-B8+ individual with acute infectious mononucleosis (IM). By stimulating peripheral blood lymphocytes with HLA-B8+ EBV-transformed B lymphoblastoid cells, the primary virus-specific CTL response was shown to include specificities for two HLA-B8-restricted antigenic determinants, FLRGRAYGL and QAKWRLQTL, which are encoded within the latent EBV nuclear antigen EBNA-3. TCR-beta sequence analysis of CTL clones specific for each epitope showed polyclonal TCR-beta repertoire selection, with structural restrictions on recognition that indicated antigen-driven selection. Furthermore, longitudinal repertoire analysis revealed long-term preservation of a multiclonal effector response throughout convalescence, with the reemergence of distinct memory T cell clonotypes sharing similar structural restrictions. Tracking the progression of specific TCR-beta clonotypes and antigen-specific TCR-V beta family gene expression in the peripheral repertoire ex vivo using semiquantitative PCR strongly suggested that selective TCR-beta expansions were present at the clonotype level, but not at the TCR-V beta family level. Overall, in this first analysis of antigen-specific TCR development in IM, a picture of polyclonal TCR stimulation is apparent. This diversity may be especially important in the establishment of an effective CTL control during acute EBV infection and in recovery from disease.

Acute Disease↗
PubMed1995

Fatal infectious mononucleosis: a severe complication in the treatment of Crohn's disease with azathioprine.

A 19 year old man with a history of Crohn's disease treated with azathioprine and prednisone, died after a primary infection with Epstein-Barr virus. He had the characteristics of the virus associated haemophagocytic syndrome, a rare complication of viral infections, which consists of fever, constitutional symptoms, hepatosplenomegaly, liver function and coagulation abnormalities, and hypertriglyceridaemia. Additionally, there was pain, cytopenia, and histiocytic hyperplasia in the bone marrow, spleen, or lymph nodes. This severe complication has been reported previously in renal transplant patients, but not in those with inflammatory bowel disease taking azathioprine. The immunosuppressive therapy may have contributed to this fatal complication of infectious mononucleosis, and this complication should be considered when treating a patient with inflammatory bowel disease with azathioprine.

Adult↗
PubMed1990

Absence of Epstein-Barr virus-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes in infectious mononucleosis.

Cytotoxic T lymphocytes (CTL) with the CD4+ phenotype that recognize major histocompatibility complex (MHC) class II antigens are detectable very frequently in cultures of human alloreactive or virus-specific T cells. The significance of these CD4+ CTL for an immune reaction in vivo is not clear. Since Epstein-Barr virus (EBV) transformed B cells express HLA-class I and class II antigens equally well both CD8+ and CD4+ CTL should be stimulated during an acute EBV infection. We analysed the MHC specificity and the phenotype of EBV-specific CTL from patients with infectious mononucleosis (IM). When tested directly without any previous culture, T cells from patients in the acute phase of IM showed specific MHC-restricted cytotoxicity against the autologous B cell line. Addition of a HLA class I specific monoclonal antibody (MoAb) but not of a HLA class II specific MoAb resulted in a complete blocking of the lytic activity. Cell sorting revealed that the entire cytotoxic activity was present in the CD8+ fraction whereas no specific CTL were detectable in the CD4+ fraction. The absence of cytotoxicity in CD4+ cells was not due to a lack of activation of these cells since both CD8+ and CD4+ cells were activated in situ, showing spontaneous growth in interleukin-2 (IL-2) and expressing the activation marker TP103. Frequency estimation revealed that 1/300-1/600 CD8+ but only 1/2000-1/4000 CD4+ T cells gave rise to a specific CTL colony after 10 days. If CD4+ colonies were tested repeatedly for cytotoxicity we found that CD4+ CTL acquired their cytotoxicity during in vitro culture. In addition, we isolated EBV-specific CD4+ T cell clones able to lyse their stimulator cells in the presence but not in the absence of lectin, even after a long period of culture. Taken together our results show that cytotoxicity mediated by CD4+ T cells does not play a role in an anti-viral immune response.

Antigens, Viral↗
PubMed1979

Hodgkin's disease in patients with previous infectious mononucleosis.

Patients with a positive reaction to the Paul-Bunnell test in the period 1961-72 were identified at nine different laboratories in Norway and matched against cases of malignant lymphoma registered at the Cancer Registry of Norway in the period 1961-75. Among 5,840 patients having a positive Paul-Bunnell test a total of six developed malignant lymphoma, three of these more than 1 year after the positive Paul-Bunnell test. The expected number of malignant lymphoma was 2.04. Of the six lymphoma cases, five were classified as Hodgkin's disease (HD). The present investigation agrees well with the findings of other epidemiological studies. There seems to be a small excess in incidence of HD among patients with previous infectious mononucleosis (IM), but both diagnostic problems and possible confounding factors must be taken into account before a possible causal association is considered.

Adolescent↗
PubMed2001

Non hypoxia-related splenic infarct in a patient with sickle cell trait and infectious mononucleosis.

Splenic infarction in patients with sickle cell trait is usually related to hypoxic conditions, while non-hypoxia-related infarcts are extremely rare. We report on a case of a 17-year-old male patient, living at sea level, who developed a severe left upper quadrant abdominal pain during the course of a febrile episode. On physical examination he had a mildly palpable but extremely painful spleen. A spleen scan revealed 2 areas of impaired radionucleide distribution. Hepatic enzymes were moderately increased and the IgM anti-EBV antibodies positive. Hemoglobin electrophoresis revealed the presence of 42% of hemoglobin S. A probable diagnosis of splenic infarction was established in a patient with sickle cell trait, during the course of infectious mononucleosis. The patient was treated symptomatically. The conditions of splenic congestion induced by the EBV infection and the high-grade fever may have contributed to splenic sequestration and subsequent infarcts.

Adolescent↗
PubMed1997

Tuning into immunological dissonance: an experimental model for infectious mononucleosis.

Virus infections cause a much more profound perturbation of the lymphoid tissue than can be accounted for by the exigencies of the antigen-specific response. The extent of this 'immunological dissonance' is seen most dramatically in mice infected with a persistent gamma-herpesvirus, MHV-68. A profile of massive, continuing proliferation of both T and B cells in the lymph nodes and spleen leads to a dramatic increase in the prevalence of a CD62Llow CD8+ T cell subset in the blood, a pattern first detected two to three weeks after intranasal exposure to the inducing virus. This syndrome, which seems identical to human infectious mononucleosis (IM), persists for a further month or more. Part of the IM-like phase of MHV-68 infection reflects the selective expansion of Vbeta4+ CD8+ T cells, with the Vbeta4 effect being apparent for several different MHC class I H-2 types but not in mice that are deficient in MHC class II glycoprotein expression. Depleting CD4(+) T helper cells in MHV-68-infected mice leads to the decreased proliferation of the CD8+ T cells in the spleen and fewer CD62Llow CD8+ T lymphocytes than would be expected in peripheral blood, but fails to diminish the prominence of the V4beta+ CD8+ population. The results so far of this unique experimental mouse model of IM suggest that both cytokine-mediated effects and a viral superantigen are operating to promote the dramatic expansion and persistence of activated CD8+ T cells in the vascular compartment.

Animals↗
PubMed1976

An outbreak of infectious mononucleosis among the personnel of an outpatient clinic.

During a four-week period, nine current or recent primary Epstein-Barr virus (EBV) infections were identified among 29 staff members of an obstetrics and gynecology outpatient clinic of an air force base hospital by EBV-specific serologic tests; i.e., early detection of IgM antibodies to EB viral capsid antigen (VCA), high titers of IgG antibodies to VCA, presence of antibodies to the D (diffuse) component of the EBV-induced early antigen (EA) complex and initial absence and later development of antibodies to the EBV-associated nuclear antigen (EBNA). Five of these individuals showed classical signs and symptoms of infectious mononucleosis (IM) so that the ratio between overt and silent infections was 1.25:1. All but one of these nine individuals gave positive monospot reactions. Three additional staff members were reported to be monospot-positive, of whom two, with prior histories of IM, had IM-like illnesses during the study period but the results of EBV-specific serologic tests were indicative of infections in the past. The EBV infections were limited to the nurses, corpsmen and administrative personnel, of whom none remained susceptible (antibody negative). The virus did not spread to the medical staff although two of the residents had no antibodies to EBV. The data indicate that under some circumstances IM may be more contagious than usually observed.

Adult↗