title: Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency.
abstract: Patients who have common variable immunodeficiency (CVID) and granulomatous/lymphocytic interstitial lung disease (GLILD) are at high risk for early mortality and B cell lymphomas. Infection with human herpes virus type 8 (HHV8), a B cell lymphotrophic virus, is linked to lymphoproliferative disorders in people who have secondary immunodeficiencies. Therefore, we determined the prevalence of HHV8 infection in CVID patients with GLILD. Genomic DNA isolated from peripheral blood mononuclear cells was screened by nested- and real time-quantitative PCR (QRT-PCR) for the presence of HHV8 genome. It was positive in 6/9 CVID patients with GLILD (CVID-GLILD), 1/21 CVID patients without GLILD (CVID-control), and no patients receiving intravenous gamma globulin (n = 13) or normal blood donors (n = 20). Immunohistochemistry (IHC) demonstrated expression of the latency-associated nuclear antigen-1 (LANA-1) in the biopsies of the lung, liver, and bone marrow of four patients with CVID-GLILD. One CVID-GLILD patient developed a B cell lymphoma during the course of the study. QRT-PCR demonstrated high copy number of HHV8 genome and IHC showed diffuse staining for LANA-1 in the malignant lymph node. HHV8 infection may be an important factor in the pathogenesis of the interstitial lung disease and lymphoproliferative disorders in patients with CVID.
authors.affiliation: Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Wheat
authors.forename: Carlyne D
authors.initials: CD
authors.lastname: Cool
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Pradeep R
authors.initials: PR
authors.lastname: Rai
authors.forename: Charles H
authors.initials: CH
authors.lastname: Kirkpatrick
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Lindenbaum
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Bates
authors.forename: Misoo C
authors.initials: MC
authors.lastname: Ellison
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Serls
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
authors.forename: John M
authors.initials: JM
authors.lastname: Routes
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000378:metabolism; D001402:B-Lymphocytes / Q000821:virology; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000401:mortality / Q000628:therapy / Q000821:virology*; D004279:DNA, Viral / Q000097:blood* / Q000235:genetics; D005260:Female; D016679:Genome, Viral; D006566:Herpesviridae Infections / Q000097:blood / Q000401:mortality / Q000628:therapy / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000235:genetics; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000401:mortality / Q000628:therapy / Q000821:virology*; D016393:Lymphoma, B-Cell / Q000097:blood / Q000401:mortality / Q000628:therapy / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; D016756:Immunoglobulins, Intravenous; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen