Monospot: a differential slide test for infectious mononucleosis

Sera collected from 372 patients with suspected infectious mononucleosis were examined for heterophile antibodies by the Paul-Bunnell and the Monospot test. Comparison of results showed the latter to be simple, time saving, and of sufficient specificity for routine use in the general laboratory.     

Studies of lymphocytotoxins in infectious mononucleosis and systemic lupus erythematosus: evidence for immune complex-mediated cytotoxicity.

The hypothesis that serum lymphocytotoxins are antigen-antibody complexes was examined. High molecular weight fractions from the sera of eighteen patients with infectious mononucleosis (IM), thirteen patients with systemic lupus erythematosus (SLE) and six healthy controls, were prepared by precipitation with polyethylene glycol 6000 (PEG). The lymphocytotoxic activity (LCA) of these PEG precipitates was significantly greater (P less than 0.01) than that of the corresponding sera and a significant correlation (r = 0.66, P less than 0.01) was observed between the LCA of sera and the PEG precipitates. In contrast to the concentration of LCA in the PEG precipitates, the heterophil antibody titres of the precipitates from IM sera were significantly less (P less than 0 05) than serum titres. Antisera raised against PEG precipitates from sera from nine patients with IM contained significant LCA. The nature of this LCA differed from that of the LCA in the original sera in temperature dependence and the molecular size. Antigen-antibody complexes in seven sera (four IM, three SLE) were dissociated at low pH (3.0) and fractionated by gel filtration at pH 3.9. The LCA of these fractions was compared with the LCA of equivalent fractions obtained by gel filtration at pH 7.2. The heterophil antibody present in sera from patients with IM and the cytotoxicity of anti-lymphocyte globulin (ALG) were used as 'antibody controls'. In this way it was shown that the LCA in patient sera, but not heterophil antibody or ALG cytotoxicity was significantly reduced (P less than 0.001) by low pH gel filtration.     

BLT-esterase in infectious mononucleosis.

Peripheral blood lymphocytes of three patients suffering from infectious mononucleosis due to Epstein-Barr virus (EBV) infection were analysed for BLT-esterase expression in peripheral blood lymphocytes by a well established cytochemical staining method. During the acute phase of disease with presence of clinical symptoms a very high level of up to 90% BLT-esterase-expressing lymphocytes were detected. The increased percentage of lymphocytes expressing BLT-esterase coincided with the time of greatest symptoms and the peak elevation of hepatocellular enzymes. The still moderately elevated level only gradually decreased to normal during the further recovery period of 2 months during which the patients described episodes of weakness. Peripheral blood lymphocyte phenotype analysis revealed a marked CD8 lymphocytosis, a CD4/CD8 ratio of about 0.2, low number of CD19+ B cells, and a high level of DR+ CD3+ lymphocytes. Reduction of BLT esterase expression during the recovery period coincided with reduction of CD8+ DR+ lymphocytes. By a combination of BLT-esterase staining with immunocytochemical phenotype analysis, 95% of CD8+ lymphocytes were found to be BLT-esterase-positive. BLT-esterase might be involved in the immunodefence against EBV in infectious mononucleosis by inducing apoptosis in EBV-transformed B cells.     

Control mechanisms in infectious mononucleosis

The blood mononuclear cells from forty-six patients with infectious mononucleosis were separated into populations of normal and atypical cells by velocity sedimentation. Both populations were characterized in terms of surface markers and response to standard mitogens. The atypical cells were of both T- and B-lymphocyte origin. Some reactivity of the normal against the freshly isolated atypical cells was detected by mixed lymphocyte reactions and ⁵¹Cr release, but this was less marked than that obtained against autochthonous lymphoblastoid cell lines. Both normal and atypical lymphocytes were stimulated by and were cytotoxic for lymphoblastoid cell-line cells. It is concluded that the atypical cells consist of two populations, a major one which is part of the host reaction to EB virus-infected cells, and a minor one which is the target for immunological responses and may represent cells transformed by virus.     

Granulocyte changes in infectious mononucleosis

Various changes in the granulocytes have been investigated in a large series of patients with infectious mononucleosis. A high proportion of cases regularly show a neutropenia with a shift to the left during the first three to four weeks of the disease; these changes, though transient, may be profound. The band cells present during the acute phase of the disease also show certain alterations in cytochemical staining and low alkaline phosphatase scores are common at this time. The maturation and release of leucocytes from the bone marrow is apparently normal. Theoretical mechanisms for the neutropenia are briefly discussed, including the possible role of excessive peripheral destruction.     

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.     

Antiphospholipid antibodies during infectious mononucleosis and their long term clinical significance

BackgroundThe prevalence of antiphospholipid antibodies (aPLs) during acute Epstein-Barr virus (EBV) infection may be as high as 30–60%. The role of these autoantibodies in the development of antiphospholipid syndrome (APS) is not clear.ObjectiveTo investigate the prevalence, persistence and clinical significance of aPLs in a series of patients diagnosed with acute EBV infection.Study designA cohort of 94 patients aged 15 or older, recently diagnosed with acute EBV was retrieved. Serum samples obtained during diagnosis were tested for the presence of aPLs and anti-β₂GP antibodies. Patients with positive sera for aPLs were assessed for the persistence of aPLs and the development of APS.ResultsThe prevalence of aPLs among 94 patients with acute EBV was 37.2%. Five of 27 available serum samples were also positive for anti-β₂ glycoprotein (anti-β₂GP) antibodies. Repeat testing for aPLs after a median of 21 months post acute infection (range 13–50 months) was performed in 17 of the 35 patients with positive aPL test. All 17 patients were found negative for aPL-IgG antibodies. Two of them had positive aPL-IgM antibodies and positive anti-β₂GP antibodies. None of the patients who had positive aPLs experienced any manifestations of APS.ConclusionThe disappearance of aPLs in the majority of the patients after acute EBV infection, along with the absence of consistent clinical findings, suggests that the detection of aPLs during acute EBV is not associated with the development APS over time.     

Transient neutrophil aggregation in a patient with infectious mononucleosis

Transient neutrophil aggregation is reported in a case of infectious mononucleosis. The phenomenon was observed on a blood film patient just before splenic infarction and decreased after splenectomy. The aggregation was so important that differential blood count could not be done. A high serum level of circulating immune complexes was found, and fluorescent spots inside of granulocytes, presumably engulfed immune complexes, could be observed. It is suggested that C activation associated with high immune complexes in infectious mononucleosis is a possible pathogenetic mechanism inducing PMNs aggregation and immune tissue damage.     

Thymic lesions in fatal infectious mononucleosis

Thymic lesions were studied in 35 patients with fatal infectious mononucleosis (FIM) including 21 males with the X-linked lymphoproliferative syndrome (XLP) and 14 non-XLP patients. Six patterns based on the lymphocyte content and status of Hassall's bodies were observed: massive lymphoproliferation effaced the architecture and Hassall's bodies (HB) in 6 cases. Epstein-Barr virus (EBV)-laden B cells surrounded by cytotoxic T cells and natural killer cells were found in one of these cases. Only 5 of the 35 thymuses contained normal-appearing HB. Seven showed a moderate reduction in HB. Rarely, multinucleated giant cells and hyaline globules were seen where one might expect HB to reside. Plasma cells and macrophages were generally abundant. Eight displayed a marked depletion of HB. In 7, no HB were recognized. Massive necrosis was seen in one of these cases. Stress involution was encountered in only two patients, both of whom had sporadic fatal IM. Thymic lesions and alterations were similar but less extensive in sporadic FIM. These morphological studies, taken in context with clinical and experimental reports, suggest that destruction of thymic epithelium may contribute to the progression of immune defects seen in XLP following EBV infection. The destruction of HB that we observed was similar in appearance to lesions in several other immune deficiency disorders.     

B lymphocytopenia in infectious mononucleosis.

Changes in lymphocyte surface markers during Epstein-Barr virus (EBV) associated infectious mononucleosis (IM) were re-examined because (1) these changes may provide information about host immune restraints to the initiation of a malignant process and (2) problems in the identification of B lymphocytes were often not appreciated in previous observations. An acute and transient reduction of IgM- and IgD-bearing B lymphocytes in the peripheral blood of these patients was demonstrated. The numbers of cells bearing Fc receptors and T lymphocytes were less consistently altered. It is hypothesized that the reduction of IgM- and IgD-bearing cells is caused by interference with the production of these cells or alternately their elimination by the virus or activated T lymphocytes.