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Previous Volume 349:1113-1122 September 18, 2003 Number 12 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Perspective by Cesarman, E. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Severe pulmonary hypertension constitutes a group of diseases characterized by complex, lumen-occluding vascular lesions that develop in genetically susceptible persons. The only viral infection associated with severe pulmonary hypertension has been that due to human immunodeficiency virus type 1, but neither the viral genome nor viral antigens have been demonstrated in pathologic lesions.

Methods We examined lung-tissue samples from 16 patients with sporadic primary pulmonary hypertension and 14 patients with secondary pulmonary hypertension for evidence of infection with human herpesvirus 8 (HHV-8). HHV-8 infection was ascertained immunohistochemically with use of an antibody directed against latency-associated nuclear antigen 1 (LANA-1), and a polymerase-chain-reaction (PCR) assay was performed on lung DNA to detect the viral cyclin gene of HHV-8. Sequence analysis was also performed.

Results In lung tissue from 10 of 16 patients with primary pulmonary hypertension (62 percent), cells within the plexiform lesions as well as cells outside the lesions were positive for LANA-1 on immunohistochemical analysis. Tissue from the same 10 patients contained viral cyclin on PCR analysis. No LANA-1 was detected in lung tissue from patients with secondary pulmonary hypertension, although one such patient had PCR evidence of viral cyclin. Plexiform lesions from patients with primary pulmonary hypertension had a histologic and immunohistochemical resemblance to cutaneous Kaposi's sarcoma lesions.

Conclusions The spectrum of trigger factors and molecular mechanisms leading to severe pulmonary hypertension and the formation of plexiform lesions is apparently wide, including both genetic and epigenetic factors. Our data suggest that infection with the vasculotropic virus HHV-8 may have a pathogenetic role in primary pulmonary hypertension.

Source Information

From the Pulmonary Hypertension Center (C.D.C., P.R.R., M.E.Y., A.E.S., T.M.B., M.W.G., N.F.V.), the Department of Pathology (C.D.C.), and the Webb-Waring Institute (D.H.-S.), University of Colorado Health Sciences Center; and the National Jewish Medical and Research Center (C.D.C., K.K.B., J.M.R.) — all in Denver; and the Cardiopulmonary Division, Department of Pathology, Johns Hopkins University, Baltimore (R.M.T.).

Drs. Rai and Yeager contributed equally to the article.

Address reprint requests to Dr. Voelkel at the Pulmonary and Critical Care Division, University of Colorado Health Sciences Center, Box C272, 4200 E. 9th Ave., Denver, CO 80262, or at norbert.voelkel{at}uchsc.edu.

Full Text of this Article

Related Letters:

HHV-8 in Pulmonary Hypertension
Henke-Gendo C., Schulz T. F., Hoeper M. M., Cool C. D., Rai P. R., Voelkel N. F.
Extract | Full Text | PDF  
N Engl J Med 2004; 350:194-195, Jan 8, 2004. Correspondence

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