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PubMed1977

Epstein-Barr virus and cytomegalovirus antibodies in infectious mononucleosis.

A method has been evolved for the demonstration of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection in 83 cases of infectious mononucleosis. Serum samples were tested for EBV IgM, anti-VCA IgG, anti-EBNA, CMV IgM and CMV IgG antibodies. An acute-phase sample (or samples) and a convalescence sample were examined in each case, and in 44 cases an additional samples was examined 5-12 months after the illness. Since the different antibodies showed characteristic differences in both titre and persistence, a reliable serodiagnosis has become possible. Acute EBV infection is characterized by the presence of EBV-VCA IgG and EBV IgG antibodies and the lack of anti-EBNA. The latter becomes demonstrable as late as the 4th to 5th month after infection. Mean age of the patients was 19 years. EBV infection was demonstrated in 65%, CMV infection in 18% of the cases. In 12% double infection seemed to be probable.

Acute Disease↗
PubMed1987

In vitro expansion of Epstein-Barr virus-specific HLA-restricted cytotoxic T cells direct from the blood of infectious mononucleosis patients.

The cytotoxic T-cell response induced by primary Epstein-Barr virus (EBV) infection and detectable in the blood of infectious mononucleosis (IM) patients shows several unusual features when tested in in vitro assays. Lysis of EBV-transformed target lines occurs with no apparent HLA restriction, and the putative EBV specificity of the response has been seriously questioned. In the present work we show that the primary T-cell response in IM is polyclonal and indeed does contain a virus-specific HLA class I antigen-restricted component, which can be selectively expanded in vitro in the presence of appropriate stimulator cells and IL-2. This allows functional analysis of the virus-specific component of the response in the absence of co-resident reactivities. Studies on blood samples taken from individuals in the acute phase of IM and again post-convalescence suggest that functionally similar populations of HLA class I-restricted cytotoxic T cells are involved in the control of both the primary and persistent phase of EBV infection.

Acute Disease↗
PubMed1976

The specificity of heterophil antibodies in patients and healthy donors with no or minimal signs of infectious mononucleosis.

Over several years sera were collected from 14 heterophil-positive students or patients who did not fulfill minimal hematologic criteria for infectious mononucleosis (I.M.) The specificity of these heterophil reactions for I.M. was investigated by determining antibodies to Epstein-Barr virus-determined antigens, i.e., to viral capsid antigens (VCA), early antigens (EA), and EBV-associated nuclear antigens (EBNA). On the basis of detectable anti-EA and/or the early absence and late emergence of anti-EBNA, four of these 14 individuals showed evidence of a current or very recent primary Epstein-Barr virus infection. The other ten patients showed antibody patterns indicative of Epstein-Barr virus infections in the past, and no firm conclusions could be drawn with regard to the specificity of their heterophil reactions. It was assumed, however, that some represented atypical clinical forms of EBV infection and that timing of specimen collection was a factor in explaining the paucity of Downey cells. In three patients, the absorbed heterophil-positive reactions persisted with little change in titer for at least 22 mo and thus might represent false-positive tests.

Adolescent↗
PubMed1983

Epstein-Barr virus, fatal infectious mononucleosis, and Hodgkin's disease in siblings.

Epstein-Barr virus (EBV) infection in a family resulted in a fatal disseminated heterophil negative infectious mononucleosis syndrome in a nine-year-old girl. This was followed closely by a similar disease process in her six-year-old brother which evolved over a one-year period into Stage IIIB Hodgkin's disease. Finally, three years after the index EBV case in the daughter, the mother was diagnosed with a non-Burkitt's-type undifferentiated lymphoma that proved rapidly fatal. The EBV involvement in the sister and brother was well documented serologically and virologically. The pathologic diagnosis was established and confirmed by more than one pathologist. There was no obvious evidence for either a specific or general immune defect in any of the family members tested. The progression of the six-year-old boy's EBV infection from a benign, yet disseminated disease process into a histopathologically confirmed case of Hodgkin's disease offers a strong suggestion that this virus was not behaving solely as a passenger. Especially relevant is the fact that the boy never fully recovered from his EBV infection and essentially became persistently infected with the virus as evidenced by his EBV-EA serology and virology results.

Adult↗
PubMed1998

Serum cytokine levels in infectious mononucleosis at diagnosis and convalescence.

Infection with the Epstein-Barr virus (EBV) is common worldwide. A significant number of infected individuals develop infectious mononucleosis (IM). IM is manifested in most patients as a benign disease with mild symptoms. However, serious complications may develop in a subset of patients. Because EBV-infected B lymphocytes produce various cytokines that may provide the cells with a proliferative advantage, cytokine concentrations in serum samples taken from IM patients were measured in order to identify the cytokines responsible for the clinical manifestations of the disease. The concentrations of interleukin-1beta (IL-1beta), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and lymphotoxin (LT) were measured using an enzyme-linked immunosorbent assay (ELISA) in serum obtained from 14 IM patients during the acute phase of the disease and during convalescence, 5 patients with identical clinical manifestations who did not have IM (sick controls), and 11 healthy volunteers. It was found that the serum levels of TNF-alpha and IL-6 were significantly high in patients with acute IM compared with the serum levels in healthy individuals (P = 0.008 and P < 0.001, respectively) but returned to normal at convalescence (P = 0.009 and P = 0.005 respectively). However, whereas TNF-alpha concentrations were significantly higher (P = 0.04) in patients with acute IM than in the sick controls, no significant difference in IL-6 concentrations was found between the two groups of patients. Changes in IL-10 concentration were not statistically significant, and IL-1beta, IL-2, IL-8, and LT were detected only sporadically. The data in this study suggest that TNF-alpha may have a specific role in causing the clinical manifestations of IM. Further studies should determine the clinical significance of TNF-alpha inhibition in IM.

Convalescence↗
PubMed2002

Transfusion-related infectious mononucleosis.

Careful donor selection has reduced but not eliminated the risk of transfusion-transmitted infections. We report a case of transfusion-related infectious mononucleosis. Given the pivotal role of Epstein-Barr virus in the development of lymphoproliferative disorders after solid-organ transplantation, its potential transmission by blood products deserves to be considered in this population.

Adult↗
PubMed1990

Expression of Epstein-Barr virus-encoded proteins and B-cell markers in fatal infectious mononucleosis.

We assessed 33 lymphoid tissues from 15 patients, including 7 with X-linked lymphoproliferative disease (XLP) and 8 patients with sporadic fatal infectious mononucleosis (IM), to determine whether the cellular infiltrate had the immunophenotype and expressed Epstein-Barr virus (EBV)-encoded proteins characteristic of either EBV-immortalized lymphoblastoid cell lines (LCL) or EBV-carrying Burkitt lymphoma (BL) cells. The results of these studies revealed that in 13 cases the proliferating B cells were polyclonal, LCL-like, and in 2 cases they were monoclonal, malignant lymphoma-like.

Adult↗
PubMed1977

Cancer incidence following infectious mononucleosis.

By means of a mailed questionnaire, the investigators examined the incidence of cancer among 2282 former college students in whom heterophile-positive infectious mononucleosis (IM) was diagnosed between 1949 and 1969 at five U.S. universities. Cancer incidence among these IM cases was compared both with national incidence rates and with an age and sex-matched group of 2779 non-IM students. No significant increase in cancer incidence was found. Three cases of Hodgkin's disease (HD) had occurred in the IM group (1.3 cases expected) and one case in the control group. All three post-IM cases of HD were in males. Intervals between diagnoses of IM and HD were three, four, and seven years, respectively. Only two other cases of lymphoma or leukemia were observed, and both were in the control group.

Adolescent↗
PubMed1993

A case of fatal infectious mononucleosis presenting with fulminant hepatic failure associated with an extensive CD8-positive lymphocyte infiltration in the liver.

We describe a fatal case of infectious mononucleosis presenting with fulminant hepatic failure associated with extensive CD8-positive lymphocyte infiltration and diffuse karyorrhexis in the liver. Immunohistochemical analysis of mononuclear cells showed that Leu-2a (CD8)-positive lymphocytes were heavily distributed in the portal areas and the sinusoidal spaces, but Leu-3a (CD4)-, Leu-14 (CD22)-, or My 4 (CD14)-positive cells were undetectable in sections of the liver. Southern blot hybridization studies disclosed the presence of Epstein-Barr virus DNA fragments in the liver tissue. The unusual pathologic and immunologic responses observed in this case could not simply be explained by severe Epstein-Barr virus infection. Some superimposed factors should be considered.

CD8 Antigens↗
PubMed2003

[Dehydrogenase activity in mononuclear cells of peripheral blood in infectious mononucleosis in children].

The study of the activity of dehydrogenases in blood cells could be an additional method at diagnostics of etiological variants of infectious mononucleosis (IM) of the viral and bacterial types. The activity of succinatedehydrogenasa (SDG) and of alpha-glycerophosphatedehydrogenase (alpha-GPDG) was increasing in lymphocytes and monocyte of the peripheral blood as compared to the same activity in healthy children. Such changes were preserved in the reconvalescense phase. The activity of enzymes in the lymphoid and monocytic cells was found at viral IM to meet the normal value. The atypical mononuclear cells, found in blood of patients with IM of both viral and bacterial nature, are a population of different-activity cellular dehydrogenases, in which cellular elements with the activity of SDG and alpha-GPDG, corresponding to the enzyme status of monocytes, are predominant.

Adolescent↗
PubMed1992

[Successful treatment of acute tubulointerstitial nephritis associated with infectious mononucleosis and causing severe uremia].

A ten years old boy with severe acute renal failure was presented. The development of acute uremia was proceeded by infectious mononucleosis. Renal biopsy revealed acute tubulointerstitial nephritis. Peritoneal- and haemodialysis was completed by steroid therapy and cytostatic treatment when glomerular proteinuria was observed. Following a 2 months uremic period the patient cured completely.

Acute Disease↗
PubMed2000

EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency.

Infection of humans with Epstein-Barr virus (EBV) may cause infectious mononucleosis (IM). Analysis of single EBV-infected cells from tonsils of IM patients for rearranged immunoglobulin genes revealed two strategies of EBV for rapid and massive spread in the B cell compartment: the direct infection of many naive as well as memory and/or germinal center B cells and the expansion of the latter cells to large clones. In IM, the generation of virus-harboring memory B cells from naive B cells passing through a germinal center reaction likely plays no role. Members of clones can show distinct morphologies and likely also EBV gene expression patterns, and this ability implies a mechanism by which EBV-harboring cells can evade immune surveillance and establish a pool of persisting EBV-infected B cells.

Adolescent↗
PubMed1986

Epstein-Barr virus infections in families: the role of children with infectious mononucleosis.

We performed a prospective evaluation of Epstein-Barr virus (EBV) infections in 78 families with a childhood index case of EBV-infectious mononucleosis (EBV-IM). During the acute index episode, adult family (household) contacts, compared with control adults, had a greater rate of oropharyngeal EBV excretion and high serum antibody responses, which suggested a recent antecedent reactivation of an old EBV infection. The increased prevalence of oropharyngeal EBV and acute serological responses found in sibling family contacts during the early surveillance period suggested that these contacts had experienced an increased rate of primary-type EBV infections shortly before or concurrent with the index case. Although nonimmune sibling contacts seroconverted at a slow rate, five of nine manifested IM with their eventual documented primary EBV infection. This study noted significant intrafamilial EBV activity surrounding an episode of childhood EBV-IM. Reactivation of an old EBV infection in adults may be an important source of virus for susceptible children within these families. Siblings of a childhood case of EBV-IM appear to be at increased risk for manifesting IM with their primary EBV infection.

Adult↗
PubMed1994

False positive EBNA IgM and IgG antibody tests for infectious mononucleosis in children.

OBJECTIVES: To assess the reliability of the Monolert test, a new enzyme-linked immunosorbent assay for the diagnosis of acute infectious mononucleosis (IM). DESIGN: A retrospective laboratory and clinical analysis of 38 children diagnosed with acute IM. SETTING: A suburban pediatric practice in Connecticut. PATIENTS: Thirty-eight children (ages 18 months to 17 years) who were diagnosed with acute IM using the Monolert test during the period October 1992 to August 1993. RESULTS: Eighty-three percent of these children had no evidence of Epstein-Barr virus infection on subsequent investigation. The false positive results of the Monolert test could not be explained on the basis of elevated antibody titers to either cytomegalovirus or Borrelia burgdorferi. CONCLUSION: Monolert is a poor screening test and is of little apparent value as a diagnostic test for acute Epstein-Barr virus infection in pediatric patients.

Acute Disease↗