Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. J Exp Med 2005 Aug 15;202(4):479-84
Date
08/17/2005Pubmed ID
16103407Pubmed Central ID
PMC2212861DOI
10.1084/jem.20050381Scopus ID
2-s2.0-23944461986 (requires institutional sign-in at Scopus site) 150 CitationsAbstract
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.
Author List
Wheat WH, Cool CD, Morimoto Y, Rai PR, Kirkpatrick CH, Lindenbaum BA, Bates CA, Ellison MC, Serls AE, Brown KK, Routes JMAuthor
John M. Routes MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAntigens, Viral
B-Lymphocytes
Common Variable Immunodeficiency
DNA, Viral
Female
Genome, Viral
Herpesviridae Infections
Herpesvirus 8, Human
Humans
Immunoglobulins, Intravenous
Lung Diseases, Interstitial
Lymphoma, B-Cell
Male
Middle Aged
Nuclear Proteins
Reverse Transcriptase Polymerase Chain Reaction