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Elevation of soluble CD23 in sera from patients with infectious mononucleosis.

CD23 is induced in B cells upon infection by Epstein-Barr virus (EBV) and a soluble form (soluble CD23: sCD23) is found in culture supernatants from EBV-transformed B cell lines. Based on these observations, we measured serum sCD23 levels in patients with infectious mononucleosis (IM) caused by EBV infection. Sera from patients with IM at the time of diagnosis contained more sCD23 than sera from normal control subjects. Changes in serum sCD23 levels during the course of disease showed that serum sCD23 levels were elevated at the time of diagnosis and they decreased to the normal levels during the convalescent phase defined by the improvement of symptoms of IM. These results indicate that the elevated levels of sCD23 were observed at the acute phase of IM and may be useful in diagnosing IM.

Adolescent↗

[Nucleic acid content in peripheral blood lymphocytes from patients with infectious mononucleosis].

An increase in RNA content in peripheral blood lymphocytes and increased number of macronuclear weakly basophilic cells (presumably due to increased content of B-lymphocytes which, in contrast to sharply basophilic T-lymphocytes, are characterized by light basophilic cytoplasm) are observed in patients with infectious mononucleosis. Macronuclear forms represented equally by hyper- and hypobasophilic elements predominate the structure of atypical mononuclears. Increased content of DNA in the peripheral blood lymphocytes is due to increased number of cells with high DNA content in the patient's blood and appearance of cells with 52-65 arb. units DNA (blast-transformed atypical mononuclears infected with the virus) which are normally absent.

Adolescent↗

Epstein-Barr virus latent membrane protein expression by Hodgkin and Reed-Sternberg-like cells in acute infectious mononucleosis.

In the light of reports of latent membrane protein (LMP) expression by Hodgkin and Reed-Sternberg (HRS) cells, paraffin sections of tonsil (two cases), lymph nodes (eight cases; three cervical, one axillary, and four inguinal) and spleen (four cases) from 14 patients with acute infectious mononucleosis (IM) have been examined for the presence of HRS-like cells and immunostained with an antibody to LMP. Sections of the tonsils and one lymph node were also stained with a panel of antibodies which characterize HRS cells of Hodgkin's disease. The tonsils contained abundant HRS-like cells, mainly adjacent to the crypts, which were highlighted by strong LMP expression. The immunophenotype of these cells closely, but not completely, resembled that of HRS cells of Hodgkin's disease. The lymph nodes and spleens showed the typical changes of acute IM but only few LMP-positive HRS-like cells were present in the cervical lymph nodes and hardly any were present in the inguinal nodes and spleen. These findings suggest that tonsillar crypt squamous epithelium may play a role in the formation of LMP-positive HRS-like cells; these cells could be progenitors of Hodgkin's disease HRS cells and, if so, this might explain the restricted sites of presentation of Hodgkin's disease.

Acute Disease↗

Rapid autologous marrow recovery and eradication of infectious mononucleosis despite severe immunosuppression following second transplantation for aplastic anemia.

A patient with aplastic anemia failed to respond to immunosuppressive therapy and first marrow transplantation (BMT). Recovery of autologous hematopoiesis was rapid following a second stem cell transplant with a non-myeloablative preparatory regimen. The autologous immune response to infectious mononucleosis (IM) 4 weeks post-transplant was normal despite recent and ongoing severe immunosuppression.

Anemia, Aplastic↗

Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus.

The present study was undertaken to unequivocally demonstrate the morphology, immunophenotype, and localization of Epstein Barr virus (EBV)-infected cells as well as the type of infection (latent versus productive) in tonsils of acute infectious mononucleosis. Paraffin sections from nine cases with clinical, serologic, and morphologic evidence of EBV infection were analyzed for the detection of small transcripts, designated EBER1 & 2, and BHLF1 by in situ hybridization (ISH) using nonisotopically labeled probes. ISH was combined with immunohistology, employing a broad panel of antibodies against B-, T-, epithelial-, macrophage-, and follicular dendritic cell (FDC)-antigens. All EBER-positive cells could be identified as lymphocytes, as they did not exhibit any morphologic or immunologic characteristics of epithelial cells, macrophages, or FDCs. A preferential accumulation of EBER-positive cells was noted around crypts, within surface squamous epithelium, and in the surroundings of necrosis. The majority of these lymphocytes could be shown to be B cells, which morphologically included Reed-Sternberg (RS)-like cells, immunoblasts, medium-sized lymphoid cells, as well as cells with plasmacytoid differentiation. In all cases, a varying number of EBER-positive T cells could be identified. ISH for BHLF1-RNA detection showed that almost all cases contained single positive small lymphoid cells, indicating a transition from latent to productive infection cycle. Such cells could also be detected within the crypt epithelium reaching up to its surface. Additional screening of 123 oropharyngeal mucosa samples from patients without evidence of acute EBV-infection, using the polymerase chain reaction for EBV-DNA detection combined with EBER- and BHLF1-ISH showed single latently infected lymphocytes in only one case. Our data imply that infected lymphocytes and not epithelial cells are, in fact, the reservoir for EBV infection, and that these are the cells that participate in the interindividual virus transfer.

Adolescent↗

Serum migration inhibitory activity and monoclonal antibody-defined T-cell phenotypes in patients with acute infectious mononucleosis.

Previous experiments in our laboratory have demonstrated that circulating endogenous leucocyte (migration) inhibitory factor (serum LIF), or a lymphokine with LIF-like activity, may be involved in the impaired cellular immune response observed during the acute phase of the Epstein-Barr virus (EBV) induced infectious mononucleosis (IM). To determine whether serum LIF activity is associated with immunoregulatory IM T-cell subset abnormalities, we analyzed the peripheral blood T-cell populations in a series of acute serum LIF-positive and LIF-negative IM patients by means of T-lymphocyte-specific monoclonal antibodies. Although there was both activation and increase of suppressor/cytotoxic T cells in all IM patients sampled in the acute stage, the relative and absolute numbers of suppressor lymphocytes were found to be significantly higher in those who had LIF activity in their serum. It is postulated that EBV infection can preferentially activate a specific T-cell subpopulation which, in its turn, inhibits the overall host immune response, possibly by a LIF-induced feedback suppression mechanism.

Antibodies, Monoclonal↗

Morphological and molecular diagnosis of a fatal form of EBV infectious mononucleosis in a child.

Mortal cases of acute Epstein-Barr virus (EBV) infection in the form of mononucleosis have been seldom described and used to be related to complications of the disease. In this report, the case of a 3-year-old girl is described, with severe form of infectious mononucleosis, deceased in the course of respiratory-circulatory insufficiency with a sudden cessation of heart action. Particular attention was given to histological lesions, phenotype of inflammatory cells and to expression of proteins and EBV RNAs (EBERs) in tissues, examined using immunocytochemical techniques and in situ hybridization. Histological patterns were dominated by massive lymphocyte infiltrates (mostly CD45RO+ and CD3+ cells), mainly in lungs and in liver and, less pronounced, in kidneys and in leptomeninx. Lymphocyte proliferation exhibited polyclonal character: both lambda and kappa chains were present. No myeloblastic differentiation could be demonstrated. The EBV proteins, as well as EBV RNAs (EBERs) were detected both in small lymphocytes B and in enlarged (blast) cells, frequently resembling Reed-Sternberg cells. In our tissue material co-expression of the two proteins (EBNA2+, LMP1+) and EBER has been demonstrated in every organ, in accordance to the latency III pattern described by other authors.

Child, Preschool↗

Spectrum of lymphoid hyperplasia: colonic manifestations of sarcoidosis, infectious mononucleosis, and Crohn's disease.

The radiographic pattern of nodular lymphoid hyperplasia, perhaps better called the lymphoid follicular pattern, has variously been described as an indication of disease and as a normal variant in the adult, with current opinion favoring the latter. We report 3 cases wherein this pattern resulted from definite pathologic processes: sarcoidosis, infectious mononucleosis, and Crohn's disease. Although usually of no pathological significance, the benign follicular pattern may reflect a variety of diseases.

Adult↗

The effect of T cells from patients with infectious mononucleosis on CFU-CGM proliferation: a preliminary report.

The neutropenia occurring during infection is a poorly understood phenomenon. Immunologically-stimulated T lymphocytes, acting upon normal bone marrow stem cells, have been etiologically implicated in several disorders. Fifteen patients, ages 17 to 25 years, and diagnosed with infectious mononucleosis by positive heterophile titers, were studied. Peripheral blood T lymphocytes were separated using sheep red blood cell rosetting. They were then cocultured with normal bone marrow cells, in a concentration of 2 X 10(4) cells/ml, in methylcellulose containing 10% colony-stimulating activity. Normal BM was obtained from patients with nonmalignant hematologic disorders, or leukemia in remission. Bone marrow cells were cultured at a concentration of 1 X 10(5) or 5 X 10(5) cells/ml, alone (control) or with T lymphocytes. Plates were incubated at 37 degrees C with 5% CO2. Colonies were scored at 14 days. Inhibition of normal, bone marrow growth was observed at both concentrations, after addition of T lymphocytes to the culture system. Such suppression was significant (p less than 0.05) for the lower concentration of normal bone marrow cells only. Variable and partial abrogation of effect was seen after overnight incubation of T lymphocytes, possibly due to loss of suppressor activity. There were insufficient numbers of tests with supernatant to allow computation of statistical significance. Correlation between T-cell ratios and suppressive effect has not been determined, although it is suspected that the responsible cells are within the T-suppressor fraction.

Adolescent↗

Antibodies to an Epstein-Barr virus nuclear antigen synthetic peptide in infectious mononucleosis. Report of two cases.

The Epstein-Barr virus nuclear antigen (EBNA-1) contains a region of repeating glycine and alanine amino acids. It has been shown that this region contains a major epitope of EBNA-1. With well-characterized sequential sera from two cases of acute infectious mononucleosis, a specific IgM response was detected to the EBNA-1 synthetic peptide by enzyme-linked immunosorbent assay (ELISA). Conversely, an IgG response was observed in the convalescent phase of the illness with a progressive decline of the IgM antibodies. This response was observed with heterophil-positive and heterophil-negative EBV/IM. The peptide-specific serologic response was confirmed by immunoblotting, the serial serum samples on extracts of EBV transformed B-cells. There was excellent correlation between the antipeptide ELISA and blotting techniques.

Acute-Phase Reaction↗

Apoptosis in infectious mononucleosis: its detection with the Beckman Coulter GenS hematology analyzer.

This article describes the potential of the Beckman Coulter GenS hematology analyzer for detecting and quantifying the phenomenon of elevated apoptosis found during the incubation at 37 degrees C of samples containing CD45RO+ reactive T-lymphocytes from patients with infectious mononucleosis (IM). Visual detection was carried out with the GenS DF1 scattergram (volume/scatter), and the means and SDs of lymphocyte positional parameters (volume, scatter, and conductivity) were recorded from the instrument research screen before and after samples were incubated in an oven for 4 hours. Thirty-one IM samples were analyzed, and the results obtained after sample incubation showed a mean reduction in lymphocyte volume of 34%, a 3.9% increase in scatter, and a 4% increase in conductivity. A new cluster of cells consistent with apoptotic lymphocytes appeared in the GenS DF1 scattergram. May-Gr-Giemsa staining and extended manual counting of the samples carried out at the same time to validate and quantify the apoptosis of the analyzed samples detected a significant increase in apoptotic cells from 1.2% (range, 0%-3%) to 8.37% (range, 1%-39%) after incubation. The same process was used to evaluate a control group of patients, and the possible interference of platelet aggregation and erythroblasts (nucleated red blood cells) in GenS apoptosis quantification was investigated. The final results showed that the appearance of the apoptotic cluster in the GenS DF1 scattergram occurred in 96.8% of the IM cases, although this phenomenon is apparently nonspecific because similar clusters appear in other pathologies, such as viral infections (hepatitis, cytomegalovirus, and acquired immune deficiency syndrome). Additional quantitative studies of apoptosis kinetics indicated that at least 4 hours of incubation are necessary. This finding has directed an investigation of apoptosis-inducing drugs (camptothecin, theophylline) to reduce incubation time and thereby enhance the practical application of automated apoptosis detection in the diagnosis of IM and other diseases in which the phenomenon of apoptosis occurs.

Adolescent↗

Spontaneous splenic rupture in mononucleosis.

Infectious mononucleosis is a disease entity with many and various manifestations. Suspicion of the disease is of the utmost importance. When indicated, adequate tests often repeated must be made to prove or disprove a suspicion of infectious mononucleosis. The disease is usually a benign condition; one of the more serious complications is "spontaneous" splenic rupture. Whether rupture is indeed spontaneous or is caused by relatively light trauma to a weakened organ is debatable. Splenectomy is the treatment for this complication; it does not cure the underlying disease. Once the diagnosis of infectious mononucleosis has been established, abdominal examinations should be limited and cautious.

Humans↗

Epstein-Barr virus infectious mononucleosis in children. II. Heterophil antibody and viral-specific responses.

An investigation was performed to address the need to establish the rate of positive heterophil antibody responses, oropharyngeal isolation of Epstein-Barr virus (EBV), and the evolving pattern of EBV-specific antibody responses among children with documented EBV-infectious mononucleosis. Findings showed that the rate of heterophil antibody responses appeared to increase progressively with advancing age from infancy up to 4 years, after which the rates approached values similar to that reported in young adult patients. The rapid slide test detected a heterophil antibody response as frequently as the Paul-Bunnell-Davidsohn horse cell test, except in children less than 4 years old. The decreased sensitivity found with the rapid slide test in the very young was associated with their less intense heterophil response. The younger group of children also developed a lower acute mean titer and, as a result, a decreased persistence of immunoglobulin M antibody to EBV-capsid antigen, whereas they had more frequent responses to EBV-early antigen directed to restricted component than both the older subjects and adults reported elsewhere. Antibodies to EBV-nuclear antigen, characteristically a late-onset antibody, tended to develop earlier than noted in adult patients. In contrast, the prevalence and continued excretion of EBV from oropharyngeal secretions was similar to that reported in adult patients. It is speculated that these age-related differences in host responses are associated with the ontogeny of the immunologic system.

Adolescent↗