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PubMed2001

Recurrent infectious mononucleosis caused by Epstein-Barr virus with persistent splenomegaly.

We present the clinical case of a 20-year-old male soldier who appeared in general good physical condition. He suffered from infectious mononucleosis caused by Epstein-Barr virus that had recurred 2 years after the first serologically documented episode. The detected splenomegaly persisted in the healthy young man, who otherwise showed no apparent immune deficiency. To our knowledge, this is an extremely rare condition.

Adult↗
PubMed1987

Epstein-Barr virus-specific transcription in normal and malignant nasopharyngeal biopsies and in lymphocytes from healthy donors and infectious mononucleosis patients.

Cytoplasmic RNA was prepared from biopsy material obtained from the nasopharynx of normal individuals and nasopharyngeal carcinoma (NPC) patients. Similar RNA preparations were prepared from lymphocytes of healthy donors and infectious mononucleosis patients. RNA was radioactively labelled in vitro and hybridized to cloned fragments of B95-8 Epstein-Barr virus (EBV). In all seropositive cases the minimum pattern of EBV-specific RNA expression was like that observed previously in latently infected, EBV-positive lymphoblastoid cell lines or Burkitt's lymphoma biopsies. A novel observation was that all of the control biopsies from normal nasopharynxes expressed EBV-specific RNA, some of which appeared to be associated with a more active state of EBV infection. The pattern of expression in NPC patients was similar to that of the normal donors but showed some variations in complexity. In general the virus-specified small RNAs were not present in normal nasopharyngeal tissue but were expressed in the NPC biopsies.

Biopsy↗
PubMed1997

Infectious mononucleosis as a disease of early childhood in Japan caused by primary Epstein-Barr virus infection.

The present study investigated 54 pediatric patients with acute Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM) in Japan. Most of the acute cases clustered within the first 5 years of life, and the peak incidence was observed at around 4 years of age. These patients were arbitrarily separated into three age groups (less than 3 years, 3-5 years, and 6-14 years). Fever, pharyngitis, lymphadenopathy and hepatomegaly were detected in more than 80% of all cases. Tonsillitis and splenomegaly were present in about 60% of cases. Skin manifestations and eyelids edema were less often detected in the older age group than in the young age groups. In addition to an increase of total white blood cell and lymphocyte counts in the peripheral blood, a significant increase in the percentage of CD3+ CD8+ HLA-DR+ T cells was always observed. Epstein-Barr virus seropositivity increased soon after birth and reached approximately 70% around 3 years of age. Close to 100% of the adult controls were EBV seropositive. The results suggest that EBV-induced acute IM is a disease of early childhood in Japan.

Adolescent↗
PubMed1978

Colonies of EBNA-positive cells in soft agar from peripheral leukocytes of infectious mononucleosis patients.

Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA)-positive lymphoblastoid cells grew as colonies in soft agar after seeding of leukocytes from the peripheral blood of four patients with infectious mononucleosis serologically determined to be caused by EBV. In individual cases more colonies were obtained from blood specimens during the acute phase of the disease than during the convalescent phase. Incorporation of human umbilical cord serum, which contained neutralizing antibody to EBV, into the agar medium did not reduce the number of colonies developing. Our observations indicate that colony-forming cells were originally present in the blood samples, and that they were not infected and subsequently transformed in vitro. Cells from less than 20% of the EBNA-positive colonies grew to form lymphoblastoid cell lines, which were EBNA-positive and had B lymphocyte surface markers. However, the majority (over 80%) of the EBNA-positive colonies failed to form immortalized cell lines. No colonies were obtained from 91 blood samples from healthy young adults and from five patients with an IM-like disease unrelated to EBV infections. The present results strongly suggest that already transformed cells or cells very easily transformed by EBV are present in the blood of IM patients.

Adult↗
PubMed2006

Prolonged illness after infectious mononucleosis is associated with altered immunity but not with increased viral load.

BACKGROUND: Primary Epstein-Barr virus (EBV) infection causes a spectrum of characteristics that range from asymptomatic seroconversion to severe infectious mononucleosis (IM), sometimes with prolonged symptoms and disability. We examined the relationships between clinical course, number of viral copies, and immunological parameters in a prospective cohort of subjects with recent IM. METHODS: Eight case patients with at least 6 months of disabling symptoms and 31 matched control subjects who had recovered promptly were included. Symptom scores were recorded at regular intervals over the course of 12 months. Cellular EBV load, EBV-specific antibody responses, lymphocyte subsets, and EBV-specific interferon (IFN)- gamma induction were measured. RESULTS: In case patients with prolonged illness, the severity of acute-phase symptoms was greater, the development of anti-EBV nuclear antigen-1 immunoglobulin G was more rapid, and the time to development of the peak IFN- gamma response to the majority of latent-cycle EBV peptides was generally slower than those in control subjects. However, in both groups, neither viral nor immune parameters correlated with the severity or duration of symptoms. CONCLUSIONS: The resolution of symptomatic IM is not determined by control of viremia, nor is it easily explained by altered host responses to EBV infection. The detailed determinants of delayed recovery remain to be elucidated.

Adolescent↗
PubMed1993

Morphological and cytochemical characteristics of atypical mononuclear cells in the blood of patients with the syndrome of infectious mononucleosis caused by Epstein-Barr virus.

On the basis of their origin and morphologic and cytochemical characteristics, atypical mononuclear cells (AMNC) in the peripheral blood of patients with the syndrome of infectious mononucleosis caused by the Epstein-Barr (EB) virus can be classified into three groups, from I to III. The AMNC groups I are the most numerous (76.36% +/- 2.50%). A larger part of these cells have the characteristics of more or less altered lymphoblasts and the smaller part of large pyroninophilic cells and "reactive immunoblasts", and meant to have developed from T lymphocytes. These are the most numerous in the acute phase of the disease, which correlates with the most significant increase of T lymphocytes values. A very high percentage (84.00% +/- 7.30%) of the AMNC group I contains acid phosphatase isoenzyme 3 and acid non-specific esterase (82.43% +/- 7.76%), a considerable percentage of beta-glucuronidase (58.75% +/- 13.99%), and acid phosphatase isoenzyme 1 (51.20% +/- 10.81%). A small percentage of these cells contains acid phosphatase isoenzyme 5 resistant to the action of L+tartaric acid. In 39.04% +/- 8.72% of the lymphocytes in the peripheral blood of the examined patients and in the two thirds and nearly three fourths of the AMNC group I, the presence of acid phosphatase manifests itself in the form of scattered granules. The positive reaction to non-specific esterase (pH 7.8-8) in 39.72% +/- 8.44% lymphocytes of the peripheral blood of the patients and in 59.26% +/- 10.09% of the AMNC group I manifests itself in the form of scattered granules.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1985

Characterization of Epstein-Barr virus-specific T-cell hybridomas derived from infectious mononucleosis.

Somatic cell hybridization was utilized to produce hybrids with surface receptors that would pertain directly to those expressed in vivo during Epstein-Barr virus (EBV) infection. Lymphocytes were obtained during acute infectious mononucleosis (IM) and fused to a double mutant of the JM human T-lymphoma cell lines. Hybrid cells that reacted with autologous EBV-infected lymphoblasts were detected by the release of Interleukin-2 into the culture medium. Reactive hybridomas also released IL-2 following coculture with allogeneic EBV-infected cells when those cells shared HLA-DR antigens of the primary parental cells. In contrast, stimulator cells with no shared HLA-DR or without evidence of EBV infection never induced IL-2 release. These results suggest the existence of a population of T cells that arise during acute IM and could account for the known proliferative phase of the disease. The requirements of IL-2 stimulation are currently under study using this system.

Herpesvirus 4, Human↗
PubMed1976

Serial serum enzyme studies in infectious mononucleosis.

Serial examinations of the white cells in the blood and serial determinations of serum glutamic oxaloacetic transaminase (GOT) and serum lactic dehydrogenase (LDH) isoenzymes have been performed in 36 patients with seropositive infectious mononucleosis. The first blood sample taken after the onset of the disease showed an increased number of mononuclear cells in the blood in 90% of the cases, elevated GOT level in 70% and elevated LDH level in 100%. Mainly isoenzymes I, II and III accounted for the elevated LDH values, while only 35% of the patients had increased LDH V (liver fraction). The number of mononuclear cells in the blood was normalized in all patients after 5 weeks and GOT normalized after 10 weeks. On the other hand, half of the patients had increased LDH, particularly isoenzymes I, II, and III, 4 months after the onset of the disease. The results indicate that the liver involvement probably is slight and of short duration, while the proliferation of lymphoid cells in the tissues, probably responsible for the main part of the LDH increase, continues for a considerably longer period.

Aspartate Aminotransferases↗
PubMedDate not supplied

[The presence of the Epstein-Barr virus in Waldeyer's lymphatic ring during the acute phase of infectious mononucleosis].

The aim of our research was to detect the existence of virus Epstein-Barr genome in the palatine- and the nasopharyngeal tonsil obtained from six patients during the acute phase of the infectious mononucleosis. The presence of EBV-DNA was demonstrated with the help of nucleic acid hybridization techniques (Southern-Blot and in situ hybridization) in the two components of the lymphoepithelial ring of the throat. The pathogenesis and the therapeutic implications of these findings are discussed.

Acute Disease↗
PubMed1990

[Infectious mononucleosis: hemolysis by autoantibodies against triosephosphate isomerase].

Generalized adenopathy and splenomegaly developed in an 18-year-old youth after a severe tonsillitis followed by headache, tiredness and weight loss for several weeks. Infectious mononucleosis (acute Epstein-Barr virus infection) was confirmed by the demonstration of virus-specific antibodies. A reticulocytosis (24%), decreased haptoglobin concentration (0.6 mg/dl) and increased lactate dehydrogenase activity (657 U/l) indicated marked haemolysis. The bone marrow showed increased erythropoiesis with abnormal maturation. Antibodies against triosephosphate isomerase and against blood group marker "i" were demonstrated in the patient's serum. Antibodies against triosephosphate isomerase from the patient's serum were purified by affinity-chromatography. They strongly reacted with the patient's erythrocytes and under complement activation induced an increased 51Cr liberation from marked erythrocytes. No corresponding effect of anti-i-antibodies was noted at 37 degrees C. With the fall in antibodies against triosephosphate isomerase the haemolysis receded and the patient became free of symptoms after 7 weeks.

Adolescent↗
PubMed1968

Infectious mononucleosis: complement-fixing antibodies to herpes-like virus associated with Burkitt lymphoma.

Complement-fixing antibodies to a herpes-like virus derived from a Burkitt tumor-cell line developed in each of 21 patients with infectious mononu-cleosis. These antibodies were absent in all serums before the patients became ill, appeared during the early phases of illness, and persisted for long periods of time. These antibodies are distinct from heterophile antibodies. None of the patients developed immune responses to herpes simplex, cytomegalo-, or reoviruses in the course of their illness. The data suggest that the development of complement-fixing antibodies to this herpes-like virus in these patients may be linked to infectious mononucleosis.

Antibodies↗
PubMed1993

Characterization of cytokine production in infectious mononucleosis studied at a single-cell level in tonsil and peripheral blood.

Cytokine profile and production was studied at a single-cell level in cells obtained from 14 patients with acute infectious mononucleosis (IM), with less than 7 days of symptomatic disease, by use of cytokine-specific MoAbs and indirect immunofluorescence technique. In producer cells, all the studied cytokines, except IL-1, accumulated in the Golgi system, which resulted in a characteristic morphology of the staining. Less than one in a thousand mononuclear cells obtained directly from IM blood and stained within 2 h of sampling produced IL-2, interferon-gamma (IFN-gamma), IL-4, IL-5, IL-6, IL-10, GM-CSF, tumour necrosis factor-alpha (TNF-alpha) or TNF-beta, spontaneously. However, these cells were induced to cytokine synthesis by T cell receptor ligation in vitro using immobilized anti-CD3 MoAbs for 2-3 h restimulation under conditions which did not activate normal cells. By this approach 168 +/- 120 cells/10,000 peripheral blood mononuclear cells produced IFN-gamma as compared with 10 +/- 8 cells/10,000 non-stimulated cultured cells obtained from IM patients (P < 0.001) and 1/10,000 cells obtained from healthy controls, respectively. No induced production of IL-2, IL-3, IL-4, IL-5, IL-10, GM-CSF or TNF-beta was detected in IM cells obtained from peripheral blood by this restimulation. In contrast, a spontaneous cytokine production was evident in tonsil material obtained from four IM patients tonsilectomized because of respiratory obstruction. From this site 160 +/- 40 cells/10,000 cells produced IL-2, 40 +/- 30 cells IL-6, 30 +/- 30 cells TNF-beta and 35 +/- 25 cells IFN-gamma, respectively. No such spontaneous IL-2, IL-6, TNF-beta or IFN-gamma production was evident in control cells obtained from patients tonsilectomized because of chronic tonsil hyperplasia.

Adolescent↗
PubMed1977

Circular Epstein-Barr virus genomes of reduced size in a human lymphoid cell line of infectious mononucleosis origin.

Circular Epstein-Barr virus (EBV) DNA molecules have been purified and characterized from a human lymphoid cell line derived from a case of heterophile antibody-positive, blood transfusion-induced infectious mononucleosis, 883L. The circular EBV DNA in three cell lines obtained by transformation of human umbilical cord blood leukocytes with a strain of EBV originally derived from 883L was also studied. As estimated from sedimentation velocity data and electron microscopy, the circular EBV DNA molecules are 10 to 15% smaller than either the circular EBV DNA previously found intracellularly in several other types of EBV-transformed cells or the linear EBV DNA present extracellularly in virus particles. In addition, the EBV-transformed cord blood cell lines studied here differed from other EBV-transformed cells in that integrated virus DNA sequences could not be detected.

Burkitt Lymphoma↗
PubMed1989

A human monoclonal autoantibody isolated from a patient with infectious mononucleosis reactive with both self antigens and Epstein-Barr virus nuclear antigen (EBNA).

In order to investigate the mechanism(s) by which Epstein-Barr virus (EBV) induces the outcome of autoantibodies during infectious mononucleosis (IM), a human IgM (k) monoclonal antibody to cytoskeletal filaments of epithelial cells has been prepared by EBV transformation of peripheral blood B lymphocytes obtained from a patient with IM. The antibody was also found to react with smooth muscle of frozen sections of human stomach tissue by immunofluorescence, and with the Epstein-Barr nuclear antigen (EBNA) by an enzyme-linked immunosorbent assay. These findings demonstrate at the clonal level the epitope homology between host's cell antigens and EBV-encoded nuclear antigen, which might have relevance in EBV-induced autoimmunity.

Antibodies, Monoclonal↗
PubMed2002

Lymph node infarction associated with infectious mononucleosis: report of a case resembling lymph node infarction associated with malignant lymphoma.

A completely infarcted lymph node should alert the pathologist to the high possibility of malignant lymphoma. The lymph node lesion of infectious mononucleosis (IM) shows marked histologic diversity and occasionally may be confused with malignant lymphoma. We report a rare case of IM showing extensive lymph node infarction whose lymph node lesion was similar to lymph node infarction associated with malignant lymphoma. This case describes a 32-year-old Japanese man who had signs and symptoms consistent with IM, which he was later proven serologically to have, but whose cervical lymph node showed extensive lymph node infarction with a thin area of granulation tissue beneath the capsule. The infarcted tissue contained numerous eosinophilic ghosts of large lymphoid cells. The thin granulation tissue was composed of numerous small lymphocytes, plasma cells, and histiocytes, in addition to large lymphoid cells including immunoblasts and granulocytes. CD20, CD3, and CD45RO immunostains revealed the mixed B- and T-cell nature of the ghosts of large lymphoid cells in the infarcted tissue as well as viable large cells in the granulation tissue. The patient was free from disease after 50 months' follow-up.

Adult↗