Detection of Herpesvirus Type 8 (HHV-8) Sequences in Patients with Kaposi's Sarcoma in Spain (1996)

To the Editor: Kaposi's sarcoma (KS) is a vascular neoplastic disorder involving spindle-cell proliferation, which manifests in several clinical forms. The classic (Mediterranean) and the endemic (African) variants are clinically similar and occur preferentially in men. Immunosuppression-associated KS develops in recipients of organ transplants who undergo immunosuppressive treatment. The epidemic form of KS presents the most aggressive clinical course and is seen almost exclusively in HIV-infected individuals. Despite differences in clinical manifestations and HIV-1 serostatus, it is more appropriate to consider all forms of KS as one entity, given the identical immunohistochemical features of the characteristic spindle cell of the tumor (1). Epidemiological studies on classic and epidemic KS strongly suggest the involvement of an infectious agent in the etiology of the neoplasm (2,3). Different microorganisms have been proposed as candidates, but none of them has been established conclusively as the causative agent (4). Recently, Chang et al. (5) have reported the presence of novel herpesvirus-like DNA sequences (referred to as herpesvirus type 8, HHV-8) in KS biopsies obtained from individuals with the epidemic form of the disease. By polymerase chain reaction (PCR) amplification, other investigators have found those sequences in the classic, endemic, and immunosuppression-associated forms (6,7). Although present in higher copy number in the KS lesions, these sequences have also been found sporadically in unaffected skin and peripheral blood cells (8). Despite the fact that these findings suggest a putative role of HHV-8 in the genesis of KS, many questions remain unanswered. Moreover, the virus has not yet been isolated. We investigated the presence of HHV-8 DNA sequences in peripheral blood lymphocytes (PBLs) obtained from 20 Spanish individuals, half of them with KS. Six were elderly and had skin lesions mainly on the legs (classical form). Two were HIV-positive homosexual men with disseminated skin lesions and visceral involvement (epidemic form). The two other patients were HIV-negative men who had KS with lung involvement in one case and disseminated cutaneous as well as mucosal lesions in the other. Neither of them recognized high-risk practices. The last patient, whose case has been reported previously (9), had a low CD4 T-cell count and fulfilled the criteria for idiopathic CD4+ T-lymphocytopenia syndrome (ICL). The 10 patients without KS included in the study as a control group had been admitted to the hospital for other pathologies, and two of them were HIV-positive homosexual men. DNA was extracted from PBLs and amplified by PCR using the HHV-8 primer pairs and conditions previously described by Chang et al. (5). Demographic characteristics and PCR results of KS cases are summarized in Table 1. Among the KS cases, PCR was positive in eight of 10 patients. None of the 10 patients without KS was positive for the HHV-8 sequences. Case 8 was particularly interesting because this subject had been previously diagnosed as having ICL. The PCR signal obtained in this case was the strongest, and the presence of a relatively higher amount of target DNA sequences in this sample was confirmed by performing serial dilutions in reactive specimens. Hypothetically, the immunosuppression observed in this individual in the absence of HIV-1 and HIV-2 infections could be related to a high HHV-8 load in his lymphocytes. Since lymphotropism is widely observed among the different members of the Herspesviridiae family and since disturbances of specific subsets of PBLs have been described in herpesvirus infections (10), a massive infection of lymphocytes by HHV-8 could explain both a deep lymphocytopenia and the development of KS in this patient. In summary, these data lend support to those reported by other investigators, favoring an association between HHV-8 and different variants of KS, regardless of the geographic origin of the patients. The presence of high amounts of virus in one HIV type 1/2-seronegative individual with KS and unexplained immunosuppression could suggest a possible involvement of the new herpesvirus in immunodeficiency syndromes. A. Heredia; A. Vallejo; I. K. Hewlett Laboratory of Molecular Virology; Division of Transfusion-Transmitted Diseases; Center for Biologies Evaluation and Research; Food and Drug Administration; Rockville, Maryland, U.S.A. V. Soriano; R. Bravo; A. Mas Service of Infectious Diseases; Instituto de Salud Carlos III; Madrid, Spain A. Castro; J. Pedreira Service of Internal Medicine; Hospital Juan Canalego; La Coruna, Spain M. Sanchez-Viera Service of Dermatology; Hospital Gregorio Mara[horizontal bar over]nón; Madrid, Spain