Symptomatic Epstein-Barr Virus Infection Research Articles

The Epstein-Barr virus (EBV) major envelope glycoprotein gp350/220-specific antibody reactivities in the sera of patients with different EBV-associated diseases.

gp350 of Epstein-Barr virus (EBV) induces a strong immune response in EBV-infected individuals, but relatively little is known about the clinical relevance of this response in patients with different EBV-associated malignancies and other diseases. Using our gp350-expressing cell clones, we studied gp350-specific humoral immune responses in the sera of individuals with nasopharyngeal carcinoma (NPC), chronic symptomatic EBV infection (CEI), Hodgkin's disease (HD), acute infectious mononucleosis (IM) and healthy EBV-seropositive individuals (HI). The titres of antibody-dependent cellular cytotoxicity (ADCC) antibodies were highest in HI followed by CEI, HD and NPC. EBV-neutralizing (NA) and gp350-specific IgG antibody profiles in these conditions were: CEI > HI > NPC > HD, whereas IgA titres were the highest in NPC sera followed by CEI and HD. The sera from IM patients were found to be negative for gp350-specific ADCC and IgA activities. Sera from HI were also negative for gp350-specific IgA. A significant positive correlation was found between serum gp350 IgA and viral capsid antigen IgA and a significant negative one between IgM and ADCC titres. High IgA titres were also found in CEI and EBV-genome positive HD in addition to NPC. Importantly, gp350-specific IgA titres were of prognostic value in NPC patients. Our data provide new insights about the clinical relevance of gp350-specific immune responses in these diseases.

Posttransplant lymphoproliferative disorders and gastrointestinal manifestations of Epstein-Barr virus infection in children following liver transplantation.

Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD). This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506). After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD. In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.

Application of in situ hybridization technique for quantitative assessment of ongoing symptomatic Epstein‐Barr virus infection after living related liver transplantation

For quantitative assessment of ongoing symptomatic Epstein‐Barr virus (EBV) infection in pediatric recipients of liver transplantation, we determined the number of peripheral blood mononuclear cells (PBMC) infected by EBV by in situ hybridization (ISH) and related the results with clinical courses of those patients. Twenty‐four patients had symptomatic EBV infection between February 1995 and March 1996. Blood samples were obtained from these 24 patients at the time of acute phase, from 13 of them during convalescence, and 37 pediatric patients before transplantation. ISH was performed on the PBMC and polymerase chain reaction (PCR) on DNA from whole blood. Oligonucleotide probes for ISH were chosen from coding sequences of EBV‐encoded small nuclear RNA 1 (EBER1). Results of ISH were reported in a number of cells expressing EBER1/5 × 104 PBMC (#EBER1). Fever, diarrhea, upper respiratory symptoms, pleural effusion, ascites, lymphadenopathy, and lymphoproliferative disease (LPD) accompanied with EBV infection proven by serology, viralspecific stain or PCR were regarded as EBV related diseases (EBVD). All samples with positive # EBER1 were accompanied by positive EBV PCR. # EBERI was 68.2±144.9 (mean ± SD) ranging from 0 to 621 in the acute phase, 0.20±0.41 ranging from 0 to 2 in the convalescence phase, 0.27 ± 0.77 in 23 preoperative patients with positive serology, and 0 in all 14 preoperative patients with negative serology. The #EBERI in ongoing EBVD was significantly greater than that of patients in convalescence or before transplantation. Patients with #EBERI greater than 10 had a significantly lower chance of convalescence and a higher mortality than patients with #EBER 1 less than 10. We conclude that # EBERI could be a specific and quantitative marker of EBVD and might predict progression to LPD.

AN INCREASED INCIDENCE OF EPSTEIN-BARR VIRUS INFECTION AND LYMPHOPROLIFERATIVE DISORDER IN YOUNG CHILDREN ON FK506 AFTER LIVER TRANSPLANTATION1

The incidence of Epstein-Barr virus (EBV) infection and lymphoproliferative disorder (LPD) was determined in a pediatric liver transplant population consisting of 51 children treated with FK506 and 91 treated with cyclosporine. The incidence of symptomatic EBV infection was 21.9% (23 of 105 cases) in children <5 yr old and 10.8% (4 of 37 cases) in children 5 to 17 yr old as compared with 2.7% (9 of 323 cases) in adults (P<0.0001). In the under 5 yr old group on cyclosporine, the incidences of EBV infection and LPD were 9 of 68 (13.2%) and 2 of 68 children, (2.9%), respectively. In contrast, in children under 5 yr old group on FK506, the incidences of EBV infection and LPD in the FK506 group were 14 of 37 (37.8%) and 7 of 37 children (18.9%), respectively. The difference between these two groups was statistically significant (P<0.02). There were no cases of LPD in the 5-17 yr-old children on either cyclosporine (n=23) or FK506 (n=14). The incidence of EBV infections in the 5 to 17 yr age group, 17.4% on cyclosporine and 0% on FK506, was less than for the younger children on FK506 (37.8%). A total of 39% (9 of 23) of children under 5 yr old who had symptomatic EBV infections developed LPD, and 44% (4 of 9) with LPD died. The higher incidence of EBV infections and LPD in the younger children treated with FK506 was probably related to a greater intensity of immunosuppression for patients on FK506 than those on cyclosporine.

AN INCREASED INCIDENCE OF EPSTEIN-BARR VIRUS INFECTION AND LYMPHOPROLIFERATIVE DISORDER IN YOUNG CHILDREN ON FK506 AFTER LIVER TRANSPLANTATION1

The incidence of Epstein-Barr virus (EBV) infection and lymphoproliferative disorder (LPD) was determined in a pediatric liver transplant population consisting of 51 children treated with FK506 and 91 treated with cyclosporine. The incidence of symptomatic EBV infection was 21.9% (23 of 105 cases) in children < 5 yr old and 10.8% (4 of 37 cases) in children 5 to 17 yr old as compared with 2.7% (9 of 323 cases) in adults (P < 0.0001). In the under 5 yr old group on cyclosporine, the incidences of EBV infection and LPD were 9 of 68 (13.2%) and 2 of 68 children, (2.9%), respectively. In contrast, in children under 5 yr old group on FK506, the incidences of EBV infection and LPD in the FK506 group were 14 of 37 (37.8%) and 7 of 37 children (18.9%), respectively. The difference between these two groups was statistically significant (P < 0.02). There were no cases of LPD in the 5-17 yr-old children on either cyclosporine (n = 23) or FK506 (n = 14). The incidence of EBV infections in the 5 to 17 yr age group, 17.4% on cyclosporine and 0% on FK506, was less than for the younger children on FK506 (37.8%). A total of 39% (9 of 23) of children under 5 yr old who had symptomatic EBV infections developed LPD, and 44% (4 of 9) with LPD died. The higher incidence of EBV infections and LPD in the younger children treated with FK506 was probably related to a greater intensity of immunosuppression for patients on FK506 than those on cyclosporine.

Symptomatic Epstein-Barr virus infection and multiple sclerosis.

In a case-control study of 214 patients with multiple sclerosis, recall of infectious mononucleosis in subjects seropositive for Epstein-Barr viral capsid antigen was associated with a relative risk of 2.9 (95% CI 1.1 to 7.2). Those who reported having infectious mononucleosis before the age of 18 years had a relative risk of multiple sclerosis of 7.9 (95% CI 1.7 to 37.9). The pathogenesis of multiple sclerosis may involve an age-dependent host response to Epstein-Barr virus infection.

Intrafamilial Transmission of Symptomatic Epstein-Barr Virus Infection among Six Adult Members of One Family

The contagiousness of Epstein-Barr virus (EBV) is low, and transmission of the disease from infected persons within a family or to other contacts is rare. We report of 6 adult members of 1 family who over a period of 6 months showed symptoms and laboratory findings compatible with acute EBV infection. Four patients examined for EBV specific antibodies had serology typical of primary EBV infection. Three of the 6 patients--1 of them serologically confirmed--were 60 years old or more, an age in which acute EBV infection is very rare.

Chronic Fatigue Syndrome and the Diagnostic Utility of Antibody to Epstein-Barr Virus Early Antigen

Antibody to Epstein-Barr virus (EBV) early antigen has been said to be the most specific indicator of symptomatic chronic EBV infection. We studied the clinical utility of this serologic test in the evaluation of patients with chronic fatigue. Thirty patients with chronic fatigue and highly elevated titers of antibody to early antigen (greater than or equal to 1:160) were compared with 30 age- and sex-matched controls with no antibody to early antigen. There were no significant differences noted between patients and controls at the initial evaluation (symptoms, physical examination, laboratory data). Follow-up information, available for 15 matched pairs, showed no differences in outcome between patients and controls. We conclude that the antibody to EBV early antigen is not helpful in the clinical evaluation of patients with chronic fatigue.

Chronic, symptomatic Epstein-Barr virus infections

Epstein–Barr virus (EBV) is a ubiquitous virus that has been implicated in a wide range of human diseases, many of which have mucocutaneous manifestations. As a member of the herpesviridae family, EBV causes lifelong infection by establishing latency in B lymphocytes. An intact immune response is critical in preventing progression of EBV disease, and the clinical manifestations of infection are dependent on the intricate relationship between virus and host immune system. This review provides a comprehensive overview of the epidemiology, pathophysiology, and diagnostic testing in EBV infection. In part I of this continuing medical education article, the mucocutaneous manifestations of EBV infection are reviewed with an emphasis on pathophysiology and management.