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PubMed1979

Characterization of thymus-derived lymphocyte subsets in acute Epstein-Barr virus-induced infectious mononucleosis.

Changes in thymus-derived (T) lymphocyte subpopulation numbers were studied in patients with acute and convalescent Epstein-Barr virus (EBV)-induced infectious mononucleosis (LM). T cell subsets were characterized by the presence of Fc receptors for IgG (TG), for IgM (TM) or by the absence of either receptor (Tnon-M, non-G). We found that in acute IM, total numbers of T and B lymphocytes were elevated (p less than 0.01). Of the T lymphocyte subsets, the total number of Tnon-M, non-G lymphocytes was increased six fold compared to normal subjects (p less than 0.001) and included the majority of the atypical T lymphocytes. The number of total TG and TM lymphocytes was moderately increased (p less than 0.05). In convalescent IM patients, the number of total T cells remained slightly elevated (p less than 0.02) whereas proportions and absolute numbers of B lymphocytes and T cell subsets returned to near normal levels. Thus, acute Epstein-Barr virus-induced IM is associated with a T lymphocytosis which is composed predominantly of atypical T cells which lack detectable Fc receptors for IgG or IgM.

Acute Disease↗
PubMedDate not supplied

Fatal infectious mononucleosis in a family.

Two male siblings, one aged five and a half months (SB), and the other aged six months (VB), with fatal infectious mononucleosis phenotype of the X-linked lymphoproliferative syndrome, which resulted in the death of both infants, are presented. Both patients had been healthy, one until the age of five and a half months, and the other until the age of six months. Then, they developed a maculopapular rash, hepatosplenomegaly and lymphadenopathy. In one sibling, the serum IgG level was low, the IgM and IgA levels were high, and the proportion of E-rosette forming cells (E-RFC) and in vitro proliferative response to PHA were normal. In the other sibling, however, the serum IgG level was normal, the IgM and IgA levels were high and the stimulation index for proliferative response to PHA was reduced due to increased spontaneous blastogenesis. Anti-EBV antibodies were negative in both siblings, except for the IgM anti-VCA in V.B. A lymph node specimen could be studied in one infant and was found to be positive for the EBV genome. Postmortem histopathological findings included the absence of cortico-medullary differentiation and identifiable Hassal's corpuscles in the thymus and depletion of T-dependent regions of lymph nodes and spleen in V.B. Atypical mononuclear cell infiltration was detected in the portal areas of the postmortem liver biopsy in S.B.

Humans↗
PubMed1970

A survey of infectious mononucleosis in the North-East Regional Hospital Board area of Scotland, 1960-9.

This report, based largely on 1258 laboratory proven cases of infectious mononucleosis (IM) detected in the North-Eastern Regional Board area of Scotland during the years 1960-9 inclusive, describes and discusses some of the epidemiological and diagnostic aspects of the disease.During the period of study, the annual rate of incidence increased fourfold from 11.1 to 44.3 cases per 100,000 population. Evidence is presented to indicate that this does not represent a true increase in prevalence but reflects improvements in disease detection. The annual incidence rates as reported by the C.D.S. for 1967-9 inclusive are regarded as a considerable underestimation of the ;true' incidence of the disease. Over a 3-year period an annual incidence equivalent to 100 per 100,000 population was found in each of two selected group practices. This value was constant and is thought to approximate the ;true' incidence of symptomatic, seropositive IM in the general community.Of the 1258 seropositive cases, 48.7% were males and 51.3% females. The peak age incidence was 15-19 years for both sexes. Twenty-one per cent of the cases were in children under 15 years and only 8.1% in adults older than 25 years. No significant variation was found in the seasonal or urban/rural incidence. Marked differences were found in the leucocyte patterns of seropositive and ;seronegative' cases.

Adolescent↗
PubMed1983

Serodiagnosis of infectious mononucleosis with a bovine erythrocyte glycoprotein.

A glycoprotein from bovine erythrocyte membrane was evaluated in two immunoassays as a reagent for the serodiagnosis of infectious mononucleosis (IM). We previously reported that a partially purified preparation of this glycoprotein, when attached to latex beads, agglutinated in the presence of IM heterophile antibody. In the present study, we used a highly purified form of the glycoprotein both as an agglutinating reagent, covalently bound to latex, and in a solid-phase sandwich-type radioimmunoassay (RIA) for IM antibody detection in a larger population of patients. We tested serum samples from college students with symptoms suggestive of IM with the latex reagent (143 samples) and with the RIA (245 samples). Correlation of these two tests, both with each other and with the classical differentially absorbed, agglutination tests for Paul-Bunnell antibody in IM sera, using fresh sheep or horse cells, was excellent (greater than 97% agreement). The new tests also corresponded in most cases with a rapid, unabsorbed preserved horse erythrocyte slide test. However, in this study of 245 samples, both apparent false-positives (5 samples) and apparent false-negatives (3 samples) were observed with this slide test. In conclusion, we found that the bovine glycoprotein as a reagent can facilitate the diagnosis of IM, giving results comparable to those with erythrocyte agglutination tests on differentially absorbed sera. The advantages are ease and speed of performance (latex test), potential for automation (RIA test), stability and uniformity of the glycoprotein reagent (latex and RIA tests), and most importantly, the ability to use unabsorbed sera (latex and RIA tests).

Animals↗
PubMedDate not supplied

Infectious mononucleosis: psychological symptoms during acute and subacute phases of illness.

Although anecdotal reports suggest that anxiety and depressive disorders may be precipitated by acute infectious mononucleosis (AIM), there are few population-based studies measuring distress and psychiatric disorder during and after infection. The purpose of this research was to study the prevalence of psychiatric disorders and psychological distress in patients with AIM at initial infection and over the subsequent 6 months. In addition, we examined the correlation of baseline biopsychosocial factors with distress at 2 and 6 months postillness. A population-based cohort with AIM was surveyed at initial infection and at 2- and 6-month follow-up visits. Measures included physical and laboratory examinations, trait and state measures of psychological and somatic distress, locus of control, social support, and functioning. Patients also received a structured psychiatric interview during the initial infection. Although transient psychological distress was common during acute infection, few patients met criteria for DSM-III-R psychiatric illness. Greater distress at 2 months was associated with significantly lower social functioning in the month prior to diagnosis and higher aspartate aminotransferase (SGOT/AST) levels, less confidence in the physician and health care system (locus of control), and less severe physical symptoms of AIM at baseline. Greater distress at 6 months was associated with an increased number of adverse life events in the 6 months after developing AIM and more days of reduced activity in the 2 weeks prior to the onset of AIM. This population-based study suggests that few subjects develop DSM-III-R psychiatric disorders with AIM. Both biological and psychosocial factors are highly correlated with psychosocial distress at 2 months, whereas psychosocial factors are more important at 6-month follow-up.

Activities of Daily Living↗
PubMedDate not supplied

Epstein-Barr virus in cerebrospinal fluid during infectious mononucleosis encephalitis.

Epstein-Barr virus (EBV) was recovered from cerebrospinal cells (but not from cell-free fluid) of a patient with meningoencephalitis complicating infectious mononucleosis. This finding suggests that virus-altered B lymphocytes can invade the central nervous system and may play a direct role in the pathogenesis of neurologic sequelae of EBV infections. Several mechanisms by which these cells can cause neurologic manifestations are discussed.

Adult↗
PubMed1977

Agammaglobulinemia with arthritis and celiac disease developing after infectious mononucleosis. Follow-up study of a case.

A previously healthy 2 1/2-year-old boy from a healthy family developed agammaglobulinemia with arthritis 3 months after infectious mononucleosis (IM). The response of serum immunoglobulins at the initial stage of IM was typical, with greatly elevated IgM and a positive IM-specific heterophil antibody test. A secondary celiac disease was diagnosed one year after IM. Considering the serum immunoglobulin levels and the normal half-lives of IgM and IgG, it seems very probable that the synthesis of immunoglobulins ceased about one month after the onset of IM. The role of suppresor T-cells in the development of acquired secondary agammaglobulinemia is discussed.

Agammaglobulinemia↗
PubMed1976

EBV-determined nuclear antigen (EBNA)-positive cells in the peripheral blood of infectious mononucleosis patients.

After removal of SRBC rosette-forming T-cells from the peripheral blood, the residual, largely B-lymphocyte fraction of five infectious mononucleosis patients was found to contain 0.5-2% blast cells, positive for the EBV-determined nuclear antigen (EBNA). There was a rough parallelism between the presence of large lymphoblasts in the hematological smear, EBNS-positive large blasts in the B-cell fraction and the ability of the T-cell fraction to exert an EBV-specific lymphocytotoxicity on established cell lines in vitro. EBNA-positive B-cells and EBV-specific killer T-cells disappeared after the acute phase of the disease.

Acute Disease↗
PubMed1981

Serological follow-up of children with infectious mononucleosis caused by Epstein-Barr virus.

Ninety children, most under 6 years of age, 73 of whom were suffering from a disease suspect of infectious mononucleosis, were examined serologically for EBV infection. Acute EBV infection was demonstrated in 40 cases. These children were followed up until the end of the second year by examining serum samples taken every month of every third month for anti-VCA-IgM, anti-VCA-IgG, anti-VCA-IgA anti-EBNA, and for the specific antibodies to the components D and R of the early antigen. Heterophil antibodies were examined by agglutination of sheep and horse erythrocytes. The temporal course of the antibody response was similar to those reported in adults while anti-EA-D and heterophil antibodies were demonstrated less frequently.

Adolescent↗
PubMed1979

EB virus-specific IgA in serum of patients with infectious mononucleosis and of healthy people of different ages.

The following sera were tested for EB virus-specific IgA: serial sera from 61 cases of infectious mononucleosis (IM) and from 195 EBV IgG positive healthy students; single sera from each of 1469 persons of different ages, 63 cases of untreated Hodgkin's disease, and 22 neonates. EBV specific IgA was found in the sera from 88% of cases of IM, from 18.5% of EBV IgG positive healthy students, and in 13.5% of repeat samples from the same students three years later. The incidence of EBV IgA varied from 5 to 30% at different ages in single sera from EBV IgG positive persons aged 2 to 70 years. The higher percentages occurred in the age groups where recent sero-conversion rates were high. Fifteen percent of sera from cases of Hodgkin's disease were positive for EBV IgA, an incidence similar to that for healthy adults in the age group 25-45 years. None of the EBV IgG positive sera from neonates gave a positive reaction for EBV IGA.

Age Factors↗
PubMed1983

Infectious mononucleosis in patients aged 40 to 72 years: report of 27 cases, including 3 without heterophil-antibody responses.

Epstein-Barr-virus (EBV)-induced infectious mononucleosis usually occurs in young adults between the ages of 15 and 30. When it occurs in older individuals, it frequently presents diagnostic problems. This report describes data from 27 such patients aged 40 to 72, all of whom had definitive evidence of a current EBV primary infection. Protracted fever, jaundice, pleural effusion, anemia, or the Guillain-Barré syndrome were dominant clinical findings among these patients. Fourteen patients were hospitalized and numerous diagnostic procedures were performed, including bone-marrow aspirations (8 patients), abdominal CAT scan procedures (4 patients), and liver (2 patients) or lymph-node biopsies (1 patient). Overall, the laboratory data in these patients were similar to those seen in young adults, with the exception of more marked hepatic dysfunction and more prominent antibody responses to the restricted (R) component of the early antigen complex. Particularly difficult were the diagnostic problems encountered in three patients in this study (3/27) who failed to develop heterophil antibodies.

Adult↗
PubMed1988

Epstein-Barr virus specific marker molecules for early diagnosis of infectious mononucleosis.

The molecular specificity of the antibody response against Epstein-Barr Virus (EBV) is studied in patients with acute primary EBV-infection, i.e. infectious mononucleosis syndrome. Using the immunoblot technique both IgM and IgG antibody responses are studied in sera obtained serially until week 20 after onset of symptoms. Healthy seropositive blood donors are used as control. Antigens are prepared from virus producer cell lines B95-8, P3HR1 and HH514-c16 (a superinducible derivative of P3HR1), induced for the expression of early antigens (EA) or viral capsid antigens (VCA) and from the EBV-negative cell lines BJAB and RAMOS. The 'WC'-serum, described by Edson et al. (J. Immunol. 130, 1983) is used to characterize EA- and VCA-specific polypeptides and to define their subcellular location. The immunoblot studies reveal an enormous diversity in EBV-specific polypeptides recognised by different individual patients, both for IgM and IgG. In addition, these patterns were markedly different from those found with control blood donor sera. The latter predominantly recognised bands at 72 kDa (EBNA) and 41 and 18 kDa respectively (both VCA components). Despite the great individual variation observed, EA-specific polypeptides at 138 kDa and at 45-52 kDa were recognised by both IgM and IgG antibodies in first serum samples of all patients tested.

Acute Disease↗
PubMed1989

Epstein-Barr virus (EBV) antigen-specific leukocyte migration inhibition in infectious mononucleosis. II. Kinetics of sensitization against five EBV-encoded nuclear proteins and the latent membrane protein.

The T cell-mediated immune response of infectious mononucleosis (IM) patients to five Epstein-Barr virus (EBV)-determined nuclear antigens, EBNAs, and to the membrane antigen associated with growth-transformed cells (latent membrane protein, LMP) was measured by the leukocyte migration inhibition (LMI) assay. Two different antigen sources were used: extracts from cells that only expressed EBNA-1, EBNA-2, or LMP after transfection with the corresponding EBV-DNA fragment, and synthetic peptides deduced from the corresponding genes. Patients in the acute phase of the disease failed to respond to EBNA-1, -5, -6, and LMP, but became responsive during convalescence. The majority of the patients responded to EBNA-2 and/or EBNA-3 in the acute phase (9/15 and 12/15, respectively). The response to EBNA-2 and/or EBNA-3 in the acute phase (9/15 and 12/15, respectively). The response to EBNA-3 disappeared more often in convalescence than the response to EBNA-2: 6 of 15 patients were negative to EBNA-2 and 12 of 15 to EBNA-3 during recovery. In addition to its value in the assessment of host sensitization to virus EBV antigens, these studies and the derived hypotheses also provide certain predictions about the predominant antigen expression in the EBV-infected host under normal and pathological conditions that can be subjected to direct experimental tests.

Adolescent↗
PubMed1996

Difficulties with the serologic diagnosis of infectious mononucleosis: a review of the RCPA quality assurance programs.

The Royal College of Pathologists of Australasia's Quality Assurance Programs (QAP) on serologic assays for infectious Mononucleosis (IM) have identified a number of important problems in laboratory diagnosis of this condition. A wide range of assays for the diagnosis of acute Epstein-Barr virus (EBV) infection are available, although heterophile antibody tests are still the most frequently performed procedures for the diagnosis of IM. In 1993, eighty-six (54%) of the 159 participating laboratories performed only a heterophile test; of these, 71% did not provide an interpretation of their results and none mentioned the need for confirmatory EBV-specific antibody testing. This revealed a lack of appreciation that heterophile tests should only be used for screening, due to their inferior sensitivity of less than 50% in children and 80-90% in adults and specificity of 95% compared to EBV-specific assays. For these reasons the use of heterophile tests is discouraged. Although EBV-specific serology has traditionally been done by immunofluorescence (IF), the use of reliable ELISA methods using purified EBV-antigens is increasing. False negative EBV VCA IgM ELISA test results were obtained by laboratories using unpurified or unspecified VCA antigens. As only five laboratories used these tests in the 1992 QAP, the tests' true performances could not be properly assessed, suggesting the need for independent studies. Variable results were obtained by laboratories using commercial EBNA IgG assays (in addition to EBV IgM) suggesting that an assessment of these kits would also be worthwhile. The QAP reaffirm that reliable EBV IgM detection is the most useful test for the diagnosis of IM, even where other EBV markers are also used. In the 1992 and 1993 QAP, laboratory performance of both heterophile and EBV-specific tests was better with non-reactive serum specimens (99% (correct) than with reactive serum specimens (90% correct).

Antibodies, Viral↗