Epstein-Barr virus-associated peripheral T-cell and NK-cell proliferative disease/lymphoma: clinicopathologic, serologic, and molecular analysis.
Peripheral T-cell proliferative disease/lymphoma is a group of diseases which exhibits heterogeneity in clinical manifestations, pathological findings and outcomes. They are highly associated with the Epstein-Barr virus (EBV) infection. It is likely that EBV plays an important role in the tumorigenesis. From January 1997 through April 2000, we identified 100 patients. One hundred healthy age- and sex- matched controls were selected. Serologic tests for the EBV infection and the study of EBV genomes in circulating non-T cells (CD3- cells), T cells (CD3+ cells), and T-cell subsets (CD4+ and CD8+ cells) were performed. The main features were prolonged fever, weight loss, hepatosplenomegaly, lymphadenopathy, multiorgan involvement, anemia, and high serum alkaline phosphatase and lactate dehydrogenase. Fifty-one patients had an aggressive course and died; median survival was 21 months. Chemotherapy was not effective in improving survival. Anti-viral capsid antigen-IgG and anti-early antigen-IgG were significantly elevated, whereas there was no significant difference in anti-EBV nuclear antigen. EBV internal repeat-1 region (IR-1) in the peripheral blood CD3+ cells was detected in 65% of the patients but in none of the controls. For the CD3- cells, EBV IR-1 was detected in 88% of the patients and 50% of the controls. Among twenty-five patients whose CD3+ cells were positive for EBV IR-1, 6 (24%) showed EBV IR-1 in only CD4+ cells, 6 (24%) in only CD8+ cells, and 13 (52%) in both CD4+ and CD8+ cells. The 30-bp deletion variant of the EBV latent membrane protein-1 gene was significantly higher in the patients than in the controls. These data support the chronic infective process. The EBV which is dormant in non-T cells may infect T cells and contribute to the pathogenesis of disease in a select group of patients.
Mitarnun
Winyou
W
Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat-Yai, Thailand 90110. miwinyou@medicine.psu.ac.th
Suwiwat
Supaporn
S
Pradutkanchana
Jintana
J
Saechan
Vannarat
V
Ishida
Takafumi
T
Takao
Satomi
S
Mori
Atsumi
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000473:pathology*; D008223:Lymphoma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000473:pathology*
D000914:Antibodies, Viral