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.
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15 August 2005
Brief Definitive Report|
August 15 2005
Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency
William H. Wheat,
William H. Wheat
1Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center
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Carlyne D. Cool,
Carlyne D. Cool
2Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
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Yoshikazu Morimoto,
Yoshikazu Morimoto
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
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Pradeep R. Rai,
Pradeep R. Rai
2Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262
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Charles H. Kirkpatrick,
Charles H. Kirkpatrick
3Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
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Barbara A. Lindenbaum,
Barbara A. Lindenbaum
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
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Christopher A. Bates,
Christopher A. Bates
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
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Misoo C. Ellison,
Misoo C. Ellison
4Department of Preventive Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
5Department of Biometrics, University of Colorado Health Sciences Center, Denver, CO 80262
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
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Amanda E. Serls,
Amanda E. Serls
2Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262
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Kevin K. Brown,
Kevin K. Brown
3Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
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John M. Routes
John M. Routes
1Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center
3Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
6Cancer Center, University of Colorado Health Sciences Center, Denver, CO 80262
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
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William H. Wheat
1Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center
Carlyne D. Cool
2Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
Yoshikazu Morimoto
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
Pradeep R. Rai
2Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262
Charles H. Kirkpatrick
3Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
Barbara A. Lindenbaum
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
Christopher A. Bates
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
Misoo C. Ellison
4Department of Preventive Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
5Department of Biometrics, University of Colorado Health Sciences Center, Denver, CO 80262
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
Amanda E. Serls
2Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262
Kevin K. Brown
3Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
John M. Routes
1Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center
3Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
6Cancer Center, University of Colorado Health Sciences Center, Denver, CO 80262
7Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206
CORRESPONDENCE John M. Routes: [email protected]
W.H. Wheat's present address is Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523.
Received:
February 18 2005
Accepted:
July 12 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 202 (4): 479–484.
Article history
Received:
February 18 2005
Accepted:
July 12 2005
Citation
William H. Wheat, Carlyne D. Cool, Yoshikazu Morimoto, Pradeep R. Rai, Charles H. Kirkpatrick, Barbara A. Lindenbaum, Christopher A. Bates, Misoo C. Ellison, Amanda E. Serls, Kevin K. Brown, John M. Routes; Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency . J Exp Med 15 August 2005; 202 (4): 479–484. doi: https://doi.org/10.1084/jem.20050381
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