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PubMed2001

[Infectious mononucleosis].

Infectious mononucleosis(IM) is a primary Epstein-Barr virus (EBV)infection. Since heterophil antibody negative IM is common in Japan, EBV antibody(presence of VCA-IgM or anti-EA, high titers of VCA-IgG in the absence of anti-EBNA) is useful for serologic diagnosis of IM. Although EBV causes the continuous growth of lymphoid cell lines in vitro and causes malignant diseases such as Burkitt lymphoma, nasopharyngeal cancer and malignant lymphomas in immunocompromised patients, IM is usually self-limiting, and after primary infection EBV persists in B cells throughout life without producing symptoms. In the present study, we studied CD8+ lymphocytes of patients with IM and demonstrate an increase in lymphocytes expressing HLA-DR and CD45RO, increase of intracellular pH, elevated plasma levels of sCD8, indicating activation of the subset. We also demonstrate activation of CD4+ T lymphocytes and gamma delta T lymphocytes. Activation of these immune systems in response to EBV is supposed to play an important role in assuring the benign course of IM.

CD4 Lymphocyte Count↗
PubMed1980

Mitotic EBNA-positive lymphocytes in peripheral blood during infectious mononucleosis.

Infectious mononucleosis (IM) is usually a benign lymphoproliferative disease caused by Epstein-Barr virus (EBV). Although EBV induces a state of continuous proliferation in infected B lymphocytes in vitro, the most prominent lymphoproliferation during IM is of activated, or atypical, T lymphocytes presumably responding to the virus or virus-infected cells. However, EBV genome-carrying cells are known to be circulating during IM, as cultured peripheral blood leukocytes from patients with the disease give rise to continuous lymphoblastoid cell lines, each cell of which contains the EBV genome and expresses the EBV determined nuclear antigen (EBNA). The proposal that EBV-infected cells in IM blood are not endowed with enhanced growth potential but are merely latently infected is supported by demonstrations that cells infected in vivo enter a viral replicative cycle when placed in vitro and that most cell lines derived from cultured lymphocytes of IM patients are infected by virus released in vitro. However the cells could also be capable of proliferation in vivo, since virus production and transformation are not mutually exclusive properties of EBV-transformed cells. Recently, EBNA has been detected in a very small fraction of peripheral blood lymphocytes of IM patients after T cells were first removed and this has been interpreted to indicate that cell transformation occurs in vivo during IM. The isolation of colonies of EBNA-positive cells from IM blood leukocytes cultures in soft agar suggests that at least some infected cells are capable of direct outgrowth into transformed cells. We report here direct evidence that circulating EBV-infected cells exhibit increased growth properties during IM.

Antibodies, Viral↗
PubMed2002

Expansion of a CD28-intermediate subset among CD8 T cells in patients with infectious mononucleosis.

Infectious mononucleosis (IM) is an acute sporadic infection that usually affects young adults, and during infection a massive expansion of CD8 T cells is generally considered to occur. However, CD28 expression of the expanded cells has not been characterized. When peripheral blood mononuclear cells of acute IM (AIM) patients were analyzed by flow cytometry, a continuous spectrum of CD28 intensity ranging from negative to high, which could be separated into CD28 negative, intermediate (int), and positive, was seen for CD8 T cells. We studied 26 IM patients who were diagnosed on the basis of standard methods and found that all patients had the continuous CD28 spectrum. CD28 is a costimulatory molecule on T cells, and its expression is associated with the subdivision of CD8 cells into cytotoxic (CD28-positive) and suppressor (CD28-negative) T cells. After 24 h of ex vivo culturing, however, the continuous spectrum was found to consist of only CD28-positive and CD28-negative CD8 T cells, because the CD28-int cells had disappeared due to apoptosis. The CD28-int T cells have several cytotoxic functions, suggesting that CD28-int T cells are effectors. Examination of other costimulatory markers in AIM patients showed that CD80 and CD152 were not affected. In patients with other viral infections, such as measles or rubella, however, the continuous spectrum was not detected. These results suggest that there is an unusual CD28 expression pattern in patients with AIM, namely, the presence of a functional CD28-int subset among CD8 T cells. These findings are of special importance for clarifying the defense mechanism against Epstein-Barr virus infection, and the role of CD28 molecules in humans and should also be helpful for the diagnosis of AIM.

Acute Disease↗
PubMed2000

Risk of Hodgkin's disease and other cancers after infectious mononucleosis.

BACKGROUND: Infectious mononucleosis, which is caused by the Epstein-Barr virus, has been associated with an increased risk for Hodgkin's disease. Little is known, however, about how infectious mononucleosis affects long-term risk of Hodgkin's disease, how this risk varies with age at infectious mononucleosis diagnosis, or how the risk for Hodgkin's disease varies in different age groups. In addition, the general cancer profile among patients who have had infectious mononucleosis has been sparsely studied. METHODS: Population-based cohorts of infectious mononucleosis patients in Denmark and Sweden were followed for cancer occurrence. The ratio of observed-to-expected numbers of cancers (standardized incidence ratio [SIR]) served as a measure of the relative risk for cancer. SIRs of Hodgkin's disease in different subsets of patients were compared with the use of Poisson regression analysis. All statistical tests including the trend tests were two-sided. RESULTS: A total of 1381 cancers were observed during 689 619 person-years of follow-up among 38 562 infectious mononucleosis patients (SIR = 1. 03; 95% confidence interval [CI] = 0.98-1.09). Apart from Hodgkin's disease (SIR = 2.55; 95% CI = 1.87-3.40; n = 46), only skin cancers (SIR = 1.27; 95% CI = 1.13-1.43; n = 291) occurred in statistically significant excess. In contrast, the SIR for lung cancer was reduced (SIR = 0.71; 95% CI = 0.58-0.86; n = 102). The SIR for Hodgkin's disease remained elevated for up to two decades after the occurrence of infectious mononucleosis but decreased with time since diagnosis of infectious mononucleosis (P: for trend <.001). The SIR for Hodgkin's disease tended to increase with age at diagnosis of infectious mononucleosis (P: for trend =.05). Following infectious mononucleosis, the SIR for Hodgkin's disease at ages 15-34 years was 3.49 (95% CI = 2.46-4.81; n = 37), which was statistically significantly higher than the SIR for any other age group (P: for difference =.001). CONCLUSION: The increased risk of Hodgkin's disease after the occurrence of infectious mononucleosis appears to be a specific phenomenon.

Adolescent↗
PubMed2007

Multiple sclerosis after infectious mononucleosis.

BACKGROUND: Infectious mononucleosis caused by the Epstein-Barr virus has been associated with increased risk of multiple sclerosis. However, little is known about the characteristics of this association. OBJECTIVE: To assess the significance of sex, age at and time since infectious mononucleosis, and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. DESIGN: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the Danish Multiple Sclerosis Registry. SETTING: Statens Serum Institut. PATIENTS: A cohort of 25 234 Danish patients with mononucleosis was followed up for the occurrence of multiple sclerosis beginning on April 1, 1968, or January 1 of the year after the diagnosis of mononucleosis or after a negative Paul-Bunnell test result, respectively, whichever came later and ending on the date of multiple sclerosis diagnosis, death, emigration, or December 31, 1996, whichever came first. MAIN OUTCOME MEASURE: The ratio of observed to expected multiple sclerosis cases in the cohort (standardized incidence ratio). RESULTS: A total of 104 cases of multiple sclerosis were observed during 556,703 person-years of follow-up, corresponding to a standardized incidence ratio of 2.27 (95% confidence interval, 1.87-2.75). The risk of multiple sclerosis was persistently increased for more than 30 years after infectious mononucleosis and uniformly distributed across all investigated strata of sex and age. The relative risk of multiple sclerosis did not vary by presumed severity of infectious mononucleosis. CONCLUSIONS: The risk of multiple sclerosis is increased in persons with prior infectious mononucleosis, regardless of sex, age, and time since infectious mononucleosis or severity of infection. The risk of multiple sclerosis may be increased soon after infectious mononucleosis and persists for at least 30 years after the infection.

Adult↗
PubMed1989

Heterophile IgM, IgA, and IgE antibodies in infectious mononucleosis.

Fifty infectious mononucleosis (IM) and 150 non-infectious mononucleosis (non-IM) sera were tested by a hemadsorption immunocapture test (HIT) for the detection of heterophile antibodies of IgM, IgA, and IgE classes. The specificity of Paul-Bunnell (PB) antibodies was ascertained by a differential absorption test. IgM PB-antibodies were demonstrated in 100% of IM sera, IgA in 92%, and IgE in 88%. PB antibodies were present only in IM sera; but other heterophile antibodies of IgM (68%), IgA (6.7%), and IgE (9.3%) classes were demonstrated in non-IM sera. IgA and IgE heterophile antibodies were thus present, especially in IM sera. HIT was found to be more sensitive than Paul-Bunnell Davidsohn test (PBD test) and suitable for the diagnosis of infectious mononucleosis.

Antibodies, Heterophile↗
PubMed2003

Infectious mononucleosis.

BACKGROUND: Infectious mononucleosis is caused by the ubiquitous Epstein-Barr virus. It is a common condition usually affecting adolescents and young adults. Most cases are mild to moderate in severity with full recovery taking place over several weeks. More severe cases and unusual complications occasionally occur. OBJECTIVE: After presenting a case of severe infectious mononucleosis, the spectrum of disease is given. Diagnosis and complications are reviewed as well as management including the possible role for antiviral medications or corticosteroid therapy. DISCUSSION: The majority of cases of infectious mononucleosis are self limiting and require only supportive care. More severe cases, although unusual, may require admission to hospital and even to an intensive care unit. Corticosteroid therapy may be indicated for severe airway obstruction or other severe complications, but should be avoided unless the benefits outweigh potential risks. Antiviral therapy has no proven benefit.

Adult↗
PubMed2003

Characteristics of Hodgkin's lymphoma after infectious mononucleosis.

BACKGROUND: Infectious mononucleosis-related Epstein-Barr virus (EBV) infection has been associated with an increased risk of Hodgkin's lymphoma in young adults. Whether the association is causal remains unclear. METHODS: We compared the incidence rates of Hodgkin's lymphoma in two population-based Danish cohorts of patients who were tested for infectious mononucleosis: 17,045 with serologic evidence of having had acute EBV infection, and 24,614 with no such evidence. We combined the cohort of patients who had serologically verified infectious mononucleosis with a cohort of 21,510 Swedish patients with infectious mononucleosis (combined total, 38,555). Biopsy specimens of Hodgkin's lymphomas occurring during follow-up in this combined cohort were tested serologically for the presence of EBV. Using this information, we modeled the relative risk of EBV-negative and EBV-positive Hodgkin's lymphoma in different periods after the diagnosis of infectious mononucleosis and estimated the median incubation time for mononucleosis-related EBV-positive Hodgkin's lymphoma. RESULTS: Only serologically confirmed infectious mononucleosis was associated with a persistently increased risk of Hodgkin's lymphoma. Sixteen of 29 tumors (55 percent), obtained from patients with infectious mononucleosis, had evidence of EBV. There was no evidence of an increased risk of EBV-negative Hodgkin's lymphoma after infectious mononucleosis. In contrast, the risk of EBV-positive Hodgkin's lymphoma was significantly increased (relative risk, 4.0; 95 percent confidence interval, 3.4 to 4.5). The estimated median incubation time from mononucleosis to EBV-positive Hodgkin's lymphoma was 4.1 years (95 percent confidence interval, 1.8 to 8.3). CONCLUSIONS: A causal association between infectious mononucleosis-related EBV infection and the EBV-positive subgroup of Hodgkin's lymphomas is likely in young adults.

Adolescent↗
PubMed1977

Immunochemical studies of infectious mononucleosis. VI. a radioimmunoassay for the detection of infectious mononucleosis heterophile antibody and antigen.

The coated-tube method of solid-phase radioimmunoassay has been adapted to the detection of heterophile antibodies and antigens of infectious mononucleosis. Disposable plastic hemagglutination trays were coated with purified glycoprotein from horse erythrocytes and the subsequent uptake of antibody from test sera was detected by radio-iodinated horse erythrocyte glycoprotein. In a preliminary survey of sera from patients with infectious mononucleosis and sera from controls, the assay proved highly sensitive and specific. The test system was also useful in a competitive binding assay for immunochemical studies of glycoproteins from other heterophile antigen-positive species.

Animals↗
PubMed2004

Gallbladder wall thickening associated with infectious mononucleosis.

Acute infectious mononucleosis is a typical self-limited lymphoproliferative illness characterized by fever, tonsillar pharyngitis, and lymphadenopathy in adolescents and young adults. Thickening of the gallbladder wall is rarely observed. We report a case of infectious mononucleosis in which marked thickening of the gallbladder wall was detected by ultrasonography and computed tomography.

Adolescent↗
PubMed2003

Predictors of fatigue following the onset of infectious mononucleosis.

BACKGROUND: Infectious mononucleosis (IM) is a risk factor for chronic fatigue. Reduced activity is the most consistent factor found to be associated with poor outcome following the onset of infectious mononucleosis. However, little is known about the biological mechanisms involved in the pathogenesis of chronic fatigue following IM and no study, so far, has examined the relation between certain illness beliefs and poor outcome. This study explored immunological, endocrine, behavioural and cognitive responses to the acute illness and assessed which components of these groups of risk factors predicted a chronic course. METHOD: Using a prospective cohort design, 71 primary care patients with IM were enrolled onto the study and interviewed. Their recovery was explored by postal questionnaire up to 1 year later. RESULTS: In the univariate analysis, increased baseline levels of immune activation were associated with fatigue at baseline and 3 months. Cortisol levels were not associated with fatigue at any point. Using multivariate models of clinical and psychosocial baseline factors, severity of symptoms and illness perceptions were found to predict fatigue 3 months later. At 6 months, fatigue was best predicted by female gender and illness perceptions, and at 12 months by female gender and a symptoms-disability factor. CONCLUSIONS: In the multivariate analysis no factors were found to predict poor outcome at all time-points. Instead the pattern of predictors changed over time, partly but not completely consistent with our a priori predictions. Larger studies are needed to explore further the predictive nature of biopsychosocial factors in the pathogenesis of chronic fatigue related to IM. The psycho-behavioural predictors found in this study are amenable to intervention. Such interventions should be tested in randomized controlled trials.

Adult↗
PubMed1978

Cellular immunity in infectious mononucleosis: I. Spontaneous and phytohaemagglutinin-induced blast transformation in infectious mononucleosis, with special reference to depressed cellular reactivity and stimulation-blocking serum factors.

Lymphocytes of patients with infectious mononucleosis (IM), EBV sero-positive subjects, patients with viral infections other than EBV, and EBV sero-negative subjects were tested for phytohaemagglutinin (PHA)-induced and spontaneous transformation in vitro. Lymphocytes of EBV sero-positive healthy subjects, tested in autologous serum, have higher spontaneous transformation than those of EBV sero-negative subjects. IM patients, in the acute phase of illness, have depressed spontaneous lymphocyte transformation, independent of serum factors. Serum factors are present in acute IM that depress spontaneous transformation further, and to a lesser extent depress reactivity to PHA. By the time the IM patients had recovered, greater than 9 weeks after onset of illness, the defects observed had disappeared.

Antibodies, Viral↗
PubMed1977

Infectious mononucleosis and mononucleosis syndromes.

Infectious mononucleosis (IM) and cytomegalovirus (CMV) mononucleosis are caused by a primary infection with related viruses, Epstein-Barr virus (EBV) and CMV. Despite the similarity of clinical manifestations, basic differences exist: (1) The heterophil antibody (HA) response is absent in CMV mononucleosis, whereas it is present in IM. (2) In IM atypical lymphocytosis reflects proliferation of B cells early and of T cells later in the disease course; in CMV mononucleosis the situation appears complex. (3) In blood, EBV is restricted to B lymphocytes, whereas CMV is found in polymorphonuclear and mononuclear leukocytes. (4) Complications of CMV mononucleosis such as hepatitis and pneumonitis may be due to virus cytopathic effect in target organs. Prominent tonsillopharyngitis with adenopathy, and visceral complications of IM are related to lymphoproliferation which is self-limited except in males with a rare familial defect in defense against EBV. Immune complex-mediated pathology may occur in both diseases. (5) CMV is frequently transmitted to a fetus in utero or to an infant during or after birth, and this occasionally leads to severe cytomegalic inclusion disease; vertical transmission of EBV appears to be exceptional. (6) Secondary EBV infections are associated with certain malignancies whereas such an association has not been recognized in the case of CMV. Toxoplasma gondii is another cause of HA-negative mononucleosis. Its complications in the heart, in skeletal muscle and in the central nervous system are related to direct invasion by the parasite. Cellular immunity plays an important role in defense against all three agents.

Cytomegalovirus Infections↗