Long-term serological follow-up of patients for Epstein-Barr virus after recovery from infectious mononucleosis.
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Adolescent↗
Biomedical subjects
W Henle
Publications and source records attributed to W Henle.
Epstein-Barr virus infection and serological profile in Greenland Eskimo children.
The Epstein-Barr virus (EBV)-specific antibody profile of 101 Greenland Eskimo children was determined. The proportion of children with serological evidence of recent or past primary EBV infections rose from 22% at 6 months of age to 79% at 24 months of age. All but 2 of 49 children more than 4 years of age proved seropositive. The geometric mean titre (GMT) of antibodies to the viral capsid antigen (VCA) was highest during the first 3 years of life and declined sharply to a lower, nearly constant level in older children. The GMT of antibodies to the nuclear antigen (EBNA), rose slowly during the first 4 years of life to its persistent level. None of the children had a history of illnesses comparable to infectious mononucleosis. The results have shown that in this population with an enhanced risk of nasopharyngeal carcinoma, primary EBV infection occurs at a very early age.
Adolescent↗
Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection.
Clinical, serologic, virologic, and immunologic evaluations for 31 adults with chronic illness and fatigue suggested that 23 had persisting Epstein-Barr virus infection. Among these 23 patients, cellular immune mechanisms were generally normal, but 4 had mild immunoglobulin deficiencies. However, 20 patients had abnormal serologic profiles specific for Epstein-Barr virus shown by significantly elevated titers of antibodies to the viral capsid antigen or early antigen, or by a deficiency of late-appearing antibodies. In 11 of 15 patients tested, circulating immune complexes were found. Circulating interferon was not found in 18 patients tested, but the activity of 2-5 oligoadenylate synthetase, an interferon-induced enzyme, was increased in 5 patients studied. Of 19 patients, 18 had persisting suppressor T-cell activity typically found in patients recovering from acute infectious mononucleosis. We believe that the Epstein-Barr virus may be associated with chronic illness in adults.
Adolescent↗
Characteristic T cell dysfunction in patients with chronic active Epstein-Barr virus infection (chronic infectious mononucleosis).
We evaluated immune functions in 16 patients with chronic active Epstein-Barr virus (EBV) infection (chronic infectious mononucleosis). Chronic infectious mononucleosis is an illness characterized primarily by chronic and occasionally disabling fatigue and other constitutional complaints, only sometimes beginning with an episode of acute infectious mononucleosis, and associated with an abnormal pattern of serum antibodies to EBV. In these patients, the frequency of circulating EBV-infected B cells that manifested spontaneous outgrowth in vitro was comparable to that found in EBV-seropositive normals, and the levels of EBV-specific suppressor activity were also normal. Upon stimulation with polyclonal activators, unseparated cells from these patients produced a relatively normal number of immunoglobulin-secreting cells. However, when purified T cells from these patients were mixed with normal mononuclear cells in co-culture, immunoglobulin production was strikingly suppressed. The degree of this T cell suppression correlated directly with the abnormally elevated titer of antibody to the early antigens of EBV. Interestingly, during normal convalescence from acute EBV-induced infectious mononucleosis a period is also seen during which T cells suppress the response of allogeneic but not autologous cells. Thus, from an immunologic viewpoint, patients with chronic active EBV infection appear "frozen" in a state typically found only briefly during the convalescence from acute EBV infection.
Adolescent↗
Epstein-Barr virus and blood transfusions.
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Antibodies, Viral↗
Immune response to Epstein-Barr virus (EBV) in ataxia-telangiectasia: EBV-specific antibody patterns and their relation to cell-mediated immunity.
Epstein-Barr virus (EBV)-specific antibody titers were investigated in 60 patients with ataxia-telangiectasia (AT) and 22 healthy members of their families. In addition, we studied 36 patients with primary immunodeficiencies, Behçet disease, and other conditions and 61 unrelated healthy controls. Twenty-seven AT patients were examined sequentially at intervals varying from 2 months to 8 years. The AT patients showed an increased incidence (66.6%) of high antibody titers (greater than or equal to 1:320) to viral capsid antigen (VCA) and also a high incidence (35%) of antibody titers to early antigens (EA), but low titers (less than 1:10) of antibodies to the EBV-associated nuclear antigen (EBNA) in 35% of the patients. The geometric mean titers (GMT) of antibodies to VCA were five to six times higher; those of anti-EBNA were five times lower in AT patients as compared with control groups. In serial determinations, anti-VCA and anti-EBNA titers remained constant with the exceptions of two patients who developed ALL and Hodgkin lymphoma. The patients with other diseases did not differ significantly from the controls, with the exception of lower titers (less than 1:10) of anti-EBNA (52.8%). AT patients with low anti-EBNA titers tended to have more advanced T-cell deficiencies than those with moderate anti-EBNA titers, as detected by total lymphocyte and E-rosetting cell counts and skin test responses. The percentage of patients with low serum IgA levels was found to be higher in the low anti-EBNA group than in the moderate anti-EBNA group (44.5 vs 20%).
Adolescent↗
Acyclovir treatment in primary Epstein-Barr virus infection. A double-blind placebo-controlled study.
Acyclovir (ACV), which effectively inhibits in vitro Epstein-Barr virus (EBV) production, was tested in 31 patients with clinical and laboratory diagnosis of infectious mononucleosis (IM) in a double-blind trial. Patients with symptoms not exceeding 7 days were randomised to intravenous ACV 10 mg/kg or placebo (PLO) treatment every 8 h for 7 days. Clinical, virological and immunological parameters were followed in each patient before, during and after treatment. There were no significant differences (p greater than 0.05) between the treatment groups for any single clinical symptom between the treatment groups. If data concerning duration of fever, weight loss, tonsillar swelling, sore throat and patient self-assessment of general health were combined, a significant effect (p less than or equal to 0.01) favouring ACV treatment was determined. ACV significantly inhibited oropharyngeal EBV shedding (p less than or equal to 0.001), but the salivary EBV titer returned within 3 weeks after cessation of treatment. Specific cellular and humoral immunity was not affected, nor was the development of virus latency.
Acyclovir↗
Quantitative analysis of immunosuppression in cyclosporine-treated heart transplant patients with lymphoma.
Lymphoma remains an important complication after heart transplantation in the era of cyclosporine immunosuppression. It has been generally assumed that the occurrence of lymphoma related to quantitative degree of immunosuppression, and this assumption is exemplified in the treatment of some such lymphomas with reduction of immunosuppression. Seventy-five consecutive survivors of heart and heart-lung transplantation between December 1980 and July 1983 were treated with cyclosporine and steroids; some received rabbit anti-thymocyte globulin for prophylaxis or treatment of rejection. Measured quantitative parameters of immunosuppression during the first three months after transplantation included mean cyclosporine level, total rabbit anti-thymocyte globulin dosage, number of days of T-cell suppression, and mean cyclosporine level during T-cell suppression. Serial Epstein-Barr virus antibody titers were measured. Lymphoma was diagnosed in six patients. The mean number of episodes of rejection did not differ between the lymphoma and the non-lymphoma groups. All quantitative measures of immunosuppression were higher in the lymphoma group, but this difference achieved statistical significance only in the case of total dosage of rabbit anti-thymocyte globulin (p less than 0.02). Four of the six lymphoma patients received some or all of their rabbit anti-thymocyte globulin dosage as prophylaxis against rejection; one received rabbit anti-thymocyte globulin solely for rejection; and the sixth received no rabbit anti-thymocyte globulin. Ebstein-Barr virus titer conversion (four-fold rise in titer) alone was not significantly associated with occurrence of lymphoma. However, logistic regression analysis suggested that Epstein-Barr virus conversion in concurrence with high mean cyclosporine levels predicted a higher risk of lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Viral↗
Humoral immune response to Epstein-Barr virus antigens and immunoglobulin allotypes in African Burkitt lymphoma patients.
We examined whether any immunoglobulin allotype was associated with an elevated risk of Burkitt's lymphoma because of the association between Burkitt's lymphoma and abnormalities of the immunoglobulin-bearing chromosomes. The distribution of Gm and Km phenotypes among 56 Burkitt lymphoma cases and 25 age-matched controls was unremarkable. Burkitt's lymphoma has also been associated with the Epstein-Barr virus, and we therefore sought a relationship between immunoglobulin allotypes and antibody response to the component antigens of the Epstein-Barr virus, VCA, EA-D, EA-R and EBNA. No immunoglobulin phenotype was associated with higher antibody titers against any antigen, but there appeared to be an interactive effect in which persons homozygous at both Gm and Km loci had elevated titers against several of the component antigens of the Epstein-Barr virus. This is the first report of an interactive effect between immunoglobulin allotypes and viruses. Antibody titers against antigens of the Epstein-Barr virus were higher in cases than in controls, as expected. However, female cases had significantly higher titers than male cases, a finding similar to that previously reported in healthy persons.
Antibody Formation↗
Epstein-Barr virus (EBV)-specific cell-mediated and humoral immune responses in ataxia-telangectasia patients.
As a part of studies on cell-mediated immune (CMI) responses of immunocompromised, Epstein-Barr virus (EBV)-infected patients who can or cannot restrict the proliferation of EBV-transformed B cells, we have studied 16 Turkish patients with ataxia-telangectasia (AT). Fifteen were EBV seropositive; one was seronegative. Among the seropositives, eight had no or only low anti-EBV-determined nuclear antigen (EBNA) antibody titers, while seven had normal anti-EBNA levels. EBV-seropositive and -seronegative healthy Turkish children were used as controls. We have particularly asked the question whether low EBNA antibody titers can be correlated with the level of EBV-specific and -nonspecific cell-mediated immunity. Non-EBV-specific tests included cell count, phenotypical characterization with monoclonal antibodies, assessment of natural killer (NK)-cell activity, and ability to suppress mitogen-induced immunoglobulin production. Two EBV-specific CMI tests were used: outgrowth inhibition (OI) and leukocyte migration inhibition (LMI). The majority of the patients of the low-EBNA antibody group was IgA deficient and had high levels of alpha-fetoprotein (a-FP). Cells reacting with OKT8 monoclonal antibody predominated in both AT patient groups. In contrast, the suppressor activity was present in only a few patients and NK and interferon-activated killing (IAK) activities were normal. EBV-specific cell-mediated responses were defective in seven of eight patients in the low-anti-EBNA group and five of seven patients in the group with normal anti-EBNA titers. It is concluded that AT patients are often defective in their EBV-specific cell-mediated immune responses and with regard to their EBNA antibody levels. These defects are associated with a predominance of T cells reacting with OKT8 monoclonal antibody.
Adolescent↗
Antineutrophil antibodies in infectious mononucleosis.
Antineutrophil antibodies were detected in the serum of 12 of 14 patients with acute Epstein-Barr virus-induced infectious mononucleosis. These antibodies were present in two patients with mononucleosis and severe neutropenia, and in 10 patients with mononucleosis uncomplicated by severe neutropenia. Antineutrophil antibodies were not detected in serum from five patients with cytomegalovirus-induced mononucleosis, or five renal allograft recipients with primary or reactivation Epstein-Barr virus infection. This study suggests that antineutrophil antibodies are among those produced by the polyclonal activation induced by Epstein-Barr virus during acute infectious mononucleosis.
Adult↗
EGNA-specific LIF production of human lymphocyte subsets.
Using the indirect leukocyte migration inhibition technique T cells have been identified as being responsible for Epstein-Barr virus nuclear antigen-induced specific leukocyte migration inhibitory factor production. The response was dependent on the presence of macrophages or their product, T-lymphocyte activating factor.
Antigens, Viral↗
T-lymphocyte subset interactions in the cell-mediated immune response to Epstein-Barr virus.
The T-lymphocyte subset interactions in the cell-mediated response to Epstein-Barr virus (EBV) were studied in an in vitro system in which the ability of T lymphocytes to inhibit outgrowth of autologous EBV-transformed B lymphocytes is assessed. Inhibition could be demonstrated within lymphocytes of both the T4 and T8 surface phenotypes. Outgrowth inhibition was observed more frequently when the effector T-cell population contained cells of both surface phenotypes. In blocking experiments the OKT3 antibody completely prevents development of outgrowth inhibitory activity; the OKT4 and OKT8 antibodies were less effective in interfering with outgrowth inhibitory function. Maximal blocking activity occurred when antibody addition occurred in the early phase of generation of suppressor function. Pharmacologically achievable concentrations of interferon-alpha restored outgrowth inhibitory activity after blocking with monoclonal antibody. EBV reactivation was easily demonstrable in a group of 10 renal allograft recipients who received OKT3 antibody for treatment of acute rejection. These studies suggest that the immunoregulatory control of proliferation of EBV-transformed B lymphocytes is complex, and involves a collaborative interaction of lymphocytes of both the T4 and T8 surface phenotypes.
Adult↗
Detection of an Epstein-Barr virus-associated membrane antigen in Epstein-Barr virus-transformed nonproducer cells by leukocyte migration inhibition and blocking antibody.
Soluble membrane fractions derived from Raji cells trigger lymphocytes of Epstein-Barr virus (EBV)-seropositive, but not EBV-seronegative, individuals to release a lymphokine that inhibits leukocyte migration. The reaction can be blocked by the sera of patients with EBV-DNA-carrying tumors, Burkitt lymphoma, or nasopharyngeal carcinoma. Absorption of these sera with EBV-positive, but not EBV-negative, cells abrogates their blocking activity. These findings suggest that the antigen responsible for the leukocyte migration inhibition reaction is an EBV-encoded or an EBV-induced membrane component. The antigen is not identical with EBV-associated nuclear antigen or any other known antibody-detected EBV antigen.
Antigens, Surface↗
Immunological characterization of Hodgkin's and non-Hodgkin's lymphoma patients with high antibody titers against Epstein-Barr virus-associated antigens.
We have studied nine Hodgkin's lymphoma (HD) and ten non-Hodgkin's lymphoma (NHL) patients with extraordinarily high anti-viral capsid antigen (VCA) titers (greater than 5120). Controls were 13 HD and 23 NHL patients with anti-VCA titers between 40 and 2560. High anti-VCA titers were present in NHL patients at the time of diagnosis or within 16 months, whereas the rise of anti-VCA titers in HD patients appeared to be a late event during the clinical course of the disease (mean time from diagnosis, 68 months). In particular, we have asked whether the exceptionally high anti-Epstein-Barr virus (EBV) titers in some HD and NHL patients can be correlated to some of the EBV-specific and -nonspecific parameters of cell-mediated immunity. The battery of non-EBV-specific immunological tests included the assessment of natural killer cell activity and the analysis of T-lymphocyte subclasses according to surface markers, together with spontaneous and mitogen-induced DNA synthesis and their helper or suppressor activity on PWM-generated immunoglobulin synthesis. Outgrowth inhibition (Ol) and leukocyte migration inhibition were used to assess EBV-specific cell-mediated immunity. The majority of the high-titer HD and NHL patients showed a drastically reduced OKT4:OKT8 ratio in their peripheral lymphocyte population. Low-titer HD and NHL patients showed no such reduction. There was no strict correlation between the number of OKT8-positive cells and suppressor activity in the functional PWM-induced immunoglobulin production test. Part of the high-titer HD patients showed defective cellular responses in the outgrowth inhibition test, directed against the proliferation of EBV-transformed (EBV-determined nuclear antigen-positive) cells. Some of them showed also a deficient leukocyte migration inhibition response to EBV-determined nuclear antigen but, interestingly, not to early antigen-VCA. In the NHL group, only one of the high-titer patients showed a similar defect. None of the low-titer HD and NHL patients showed such defects.
Adult↗
Epstein-Barr virus-associated antibody pattern in untreated non-Hodgkin lymphoma patients. Relationship to clinical variables and lymphocyte functions.
Sera from 296 unselected and untreated patients with non-Hodgkin lymphoma (NHL) classified according to the Rappaport and the Kiel systems were analyzed for antibodies to Epstein-Barr virus (EBV). The aim of the study was to determine whether antibody spectra and titers to EBV-coded antigens correlated to clinical and immunological variables and whether the titers were of any prognostic significance. Increased antibody titers to EB viral capsid antigen (VCA) and slightly raised titers to early antigens (EA) of the diffuse (D) and restricted (R) types were noted frequently. Anti-VCA antibody titers correlated to clinical stage and age of the patients but not to histological subgroups according to the Rappaport or the Kiel classification systems. However, anti-VCA titers greater than or equal to 1:2560 were seen only in diffuse lymphomas according to the Rappaport and in non-follicle cell-derived lymphomas according to the Kiel classifications. Patients with complement-receptor-positive diffuse lymphomas had higher anti-VCA titers than complement-receptor-positive nodular cases. Anti-VCA titers also correlated positively to serum IgG levels (p less than 0.01). Total number of lymphocytes separated from peripheral blood and mitogen induced (ConA, PWM) DNA synthesis were recorded before treatment in 56 of the patients. The patients exhibited a significant lymphocytopenia as well as a significantly reduced lymphocyte response to mitogens (p less than 0.001) compared to healthy controls. Elevated anti-VCA titers and anti-EA titers correlated to a good mitogen-induced lymphocyte response (p less than 0.05). Only anti-D 1:40 at diagnosis predicted a poor prognosis.
Adolescent↗
Enzyme-linked immunosorbent assay for the detection of Epstein-Barr virus-induced antigens and antibodies.
Two Epstein-Barr virus (EBV)-specific ELISA tests were developed. One, based on the use of crude extracts from virus producer cells highly induced in the presence of Ara C (providing EA + VCA- cells) or in the absence of the drug (providing EA + VCA + cells) is suitable for the detection of antibodies directed against antigen complexes associated with the lytic virus cycle; i.e., EA, VCA and presumably also MA. The second, performed with purified EBNA, can be used for the detection of antibodies to the transformation-associated nuclear antigen. The tests are expected to find application in the dissection of antibody responses of patients to various antigenic subcomponents, the monitoring of EBV-coded antigens during biochemical purification, and the screening of spent media from hybridoma cultures for EBV-specific antibodies.
Antibodies, Viral↗
Epstein-Barr virus-specific serodiagnostic tests in carcinomas of the head and neck.
Sera from 256 patients with cancers of the head and neck were examined for their profiles of IgG and IgA antibodies to Epstein-Barr virus (EBV)-specific, viral capsid antigen (VCA), the diffuse (D) and the restricted (R) components of the early antigen (EA) complex, and the EBV-associated nuclear antigen (EBNA), in order to assess the value of these procedures in the routine diagnosis of poorly or undifferentiated nasopharyngeal carcinoma (NPC). In 13 NPC patients, the carcinoma had invaded cervical lymph nodes, and their sera revealed, in addition to high IgG anti-VCA titers, elevated levels of IgA antibodies to VCA, of IgG antibodies to D, and most also had IgA anti-D. Such profiles were seen in very few of the patients with carcinomas at other sites of the head and neck. They had not developed in four NPC patients whose tumors were limited to the postnasal space, and in three patients with other tumors at that site. Among 15 patients with cervical node metastases from occult primary tumors, 2 had EBV-specific antibody profiles compatible with NPC, 1 was judged to have NPC on clinical grounds, and the other died of a pulmonary carcinoma, or possibly pulmonary metastases. In 4 of the remaining 13 patients with occult tumors, the primary site was found outside the nasopharynx, whereas it escaped detection in the other 9. These results lend further support to the usefulness of the EBV-specific serology to clinicians in the diagnosis of NPC, especially in cases of lymph node invasion by undetected primary tumors. The data also emphasize the need of complementing the serology with the examination of biopsies for the presence of EBV deoxyribonucleic acid (DNA) or, more readily performed, EBNA-positive carcinoma cells.
Aged↗