Mannose-binding lectin genotypes and susceptibility to epstein-barr virus infection in infancy.

In a cohort study of children < 4 years of age in Greenland, mannose-binding lectin (MBL2) genotypes and Epstein-Barr virus (EBV) antibody levels were determined. EBV seropositivity was significantly lower and time to seroconversion increased in MBL-insufficient compared with MBL-sufficient children, indicating that MBL may be involved in primary EBV infection in infancy.

Viruses and Hodgkin lymphoma: no evidence of polyomavirus genomes in tumor biopsies.

The epidemiology of young adult Hodgkin lymphoma (HL) suggests that delayed exposure to a common childhood pathogen may be involved in disease pathogenesis. The Epstein-Barr virus (EBV) is associated with a proportion of cases but cases of young adult HL in westernized countries are less frequently EBV-associated than cases in other age groups and geographical locales. This study investigated the possibility that polyomaviruses might be involved in the etiology of HL by analysing a series of 35 cases of classical HL using both specific and degenerate PCR assays for polyomavirus genomes. No positive results were obtained, indicating that it is highly unlikely that this virus family is directly involved in the pathogenesis of HL.

Impact of tumor Epstein-Barr virus status on presenting features and outcome in age-defined subgroups of patients with classic Hodgkin lymphoma: a population-based study.

The association between tumor Epstein-Barr virus (EBV) status and clinical outcome in Hodgkin lymphoma (HL) is controversial. This population-based study assessed the impact of EBV status on survival in age-stratified cohorts of adults with classic HL (cHL). Data from 437 cases were analyzed with a median follow-up of 93 months. Overall survival (OS) was significantly better for EBV-negative compared with EBV-positive patients (P < .001), with 5-year survival rates of 81% and 66%, respectively; disease-specific survival (DSS) was also greater for EBV-negative patients (P = .03). The impact of EBV status varied with age at diagnosis. In patients aged 16 to 34 years, EBV-associated cases had a survival advantage compared with EBV-negative cases, but differences were not statistically significant (P = .21). Among patients 50 years or older, EBV positivity was associated with a significantly poorer outcome (P = .003). Excess deaths occurred in EBV-positive patients with both early- and advanced-stage disease. In multivariate analysis of OS in the older patients, EBV status retained statistical significance after adjusting for the effects of sex, stage, and B symptoms (P = .01). Impaired immune status may contribute to the development of EBV-positive cHL in older patients, and strategies aimed at boosting the immune response should be investigated in the treatment of these patients.

Phenotype and frequency of Epstein-Barr virus-infected cells in pretreatment blood samples from patients with Hodgkin lymphoma.

An accumulating body of data suggests that the Epstein-Barr virus (EBV), a lymphotropic herpesvirus, is involved in the pathogenesis of a proportion of cases of Hodgkin lymphoma (HL). In this study, we showed that the frequency of circulating EBV-infected cells was significantly higher (P < 0.001) in pretreatment blood samples from EBV-associated cases when compared with non-EBV-associated cases. We further showed that in patients with EBV-associated disease, the virus persisted in the peripheral blood in memory B cells. This phenotype is consistent with that seen in healthy seropositive controls, post-transplant patients and patients with acute infectious mononucleosis. The data suggest that an increased frequency of EBV carrying B cells in peripheral blood is associated with EBV-associated HL.

An epidemiologic study of index and family infectious mononucleosis and adult Hodgkin's disease (HD): evidence for a specific association with EBV+ve HD in young adults.

Infectious mononucleosis (IM) is an established risk factor for Hodgkin's disease (HD). A substantial minority (33%) of cases of HD have Epstein-Barr virus (EBV) DNA within the malignant cells (are EBV+ve). It is unclear whether risk after IM applies specifically to EBV+ve HD. We report the results of a population-based case-control study of HD in adults (n = 408 cases of classical HD, 513 controls) aged 16-74 years; the case series included 113 EBV+ve and 243 EBV+ve HD. Analyses compared total HD, EBV+ve HD and EBV-ve HD with the controls and EBV+ve HD with EBV-ve HD cases using, mainly, logistic regression. Regression analyses were adjusted for gender, age-group and socioeconomic status, and were performed for the whole age range and separately for young (< 35 years) and old adults (> or = 35 years); formal tests of effect modification by age were included. For the young adults, reported IM in index or relative was strongly and significantly associated with EBV+ve HD when compared to controls (odds ratio [OR] = 2.94, 95% confidence interval [CI]: 1.08-7.98 and OR = 5.22, 95% CI: 2.15-12.68, respectively). These results may be interpreted as indications that late first exposure to EBV increases risk of HD, especially in young adults; this applies primarily to EBV+ve HD.

Hodgkin lymphoma and Epstein-Barr virus (EBV): no evidence to support hit-and-run mechanism in cases classified as non-EBV-associated.

The Epstein-Barr virus (EBV) is associated with a proportion of Hodgkin lymphoma (HL) cases, and this association is believed to be causal. The aetiology of cases lacking EBV in the tumour cells (EBV HRS-ve), which make up the majority of cases in western countries, is obscure. It has been suggested that EBV may also cause these tumours by using a hit-and-run mechanism. Support for this idea comes from the finding that most young adult patients, who are likely to have a good immune response to EBV, have EBV HRS-ve HL. We investigated this possibility using a combined serologic and molecular approach. Analysis of EBV seroprevalence rates in an epidemiologic study of young adult HL revealed that cases with EBV HRS-ve HL were more likely to be EBV-seronegative than controls. Furthermore, additional studies clearly showed that some HL patients have never been infected by EBV. Quantitative PCR was used to look for the presence of deleted EBV genomes in a series of adult cases with both EBV HRS+ve and HRS-ve HL. Subgenomic fragments were detected in equimolar proportions. This study, therefore, found no evidence to support the idea that a hit-and-run mechanism involving EBV plays a role in the pathogenesis of HL.

Viruses and Hodgkin disease: no evidence of novel herpesviruses in non-EBV-associated lesions.

The Epstein-Barr virus (EBV) is associated with a proportion of cases of Hodgkin disease (HD) and this association is believed to be causal. Epidemiological studies suggest that an infectious agent is involved in the aetiology of young adult HD, however, cases in this age group are less likely to have EBV-associated disease than cases diagnosed in early childhood or older adult years. Molecular studies have failed to find a consistent association between HD and other candidate viruses, and the aetiology of non-EBV-associated cases remains obscure. We looked for evidence of herpesvirus infection in samples of non-EBV-associated HD using a highly sensitive, degenerate PCR assay. Despite exhaustive sequence analysis of PCR products, no novel herpesviruses were identified. These results suggest that it is extremely unlikely that a novel herpesvirus is involved in the pathogenesis of non-EBV-associated HD.