title: Serologic and molecular evidence for a possible pathogenetic role of viral infection in CD3-negative natural killer-type lymphoproliferative disease of granular lymphocytes.
abstract: We studied a series of 18 patients with CD3- lymphoproliferative disease of granular lymphocytes (LDGL) for evidence of chronic viral infection, including Epstein-Barr (EBV), hepatitis B (HBV), hepatitis C (HCV), human T lymphotropic virus (HTLV), and human immunodeficiency virus (HIV). Although all patients tested had serologic evidence for past infection with EBV, polymerase chain reaction (PCR) analysis of peripheral blood mononuclear cell (PBMC) DNA utilizing specific EBV primers demonstrated the presence of EBV-DNA in only six of 17 CD3- LDGL cases. A previous history of HBV infection, as defined by the presence of circulating IgG anti-HBc antibodies associated with either HBsAg positivity or negativity, was documented in seven cases; however, viral DNA was not detected in PBMC of these patients using PCR with specific HBV primers. Specific anti-HCV antibodies, confirmed by recombinant immunoblot assay, were detected in five CD3- LDGL patients; PCR analysis demonstrated the presence of viral RNA in PBMC of two of these cases. No patient had antibodies to HTLV-I/II or HIV-1/2. Five patients were infected by more than one virus (two with HBV and EBV and three with HBV and HCV). Our results provide serologic evidence for past viral infection in the large majority of CD3- NK-type LDGL patients. These data suggest that viral infection may have played a role early in disease pathogenesis and may no longer be necessary in sustaining GL proliferation in CD3- NK-type LDGL.
authors.affiliation: Department of Clinical Medicine, Padua University School of Medicine, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Zambello
authors.forename: T P
authors.initials: TP
authors.lastname: Loughran
authors.forename: L
authors.initials: L
authors.lastname: Trentin
authors.forename: P
authors.initials: P
authors.lastname: Pontisso
authors.forename: L
authors.initials: L
authors.lastname: Battistella
authors.forename: R
authors.initials: R
authors.lastname: Raimondi
authors.forename: M
authors.initials: M
authors.lastname: Facco
authors.forename: R
authors.initials: R
authors.lastname: Sancetta
authors.forename: C
authors.initials: C
authors.lastname: Agostini
authors.forename: G
authors.initials: G
authors.lastname: Pizzolo
mesh_terms: D000956:Antigens, Viral / Q000097:blood; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D006800:Deltaretrovirus Infections / Q000150:complications; D015658:HIV Infections / Q000150:complications; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006566:Herpesviridae Infections / Q000150:complications; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D014412:Tumor Virus Infections / Q000150:complications; D014777:Virus Diseases / Q000150:complications* / Q000276:immunology / Q000821:virology
chemical_list: D000956:Antigens, Viral; D017252:CD3 Complex; D004279:DNA, Viral; D012367:RNA, Viral