Abstract
Independent epidemiologic studieshave shown a strong association be-tween Kaposi’s sarcoma (KS) and infec-tion with human herpesvirus 8 (HHV-8or KSHV). HHV-8 genomic sequenceshave been found in all forms (1–5)andall histologic stages (6) of KS, with viralDNA being localized to tumor endothe-lial cells and spindle cells (7,8). Detec-tion of HHV-8 DNA sequences in theperipheral blood of patients who are se-ropositive for human immunodeficiencyvirus 1 (HIV) is a strong predictor ofprogression to KS (9,10). The vast ma-jority of patients with KS have antibod-ies against HHV-8(11–14), with sero-conversion before clinical disease (15).HHV-8 infection is apparently not com-mon in the general population of theU.K. and the United States, but it iscommon in groups at high risk for KS(11–14).In addition, HHV-8 seropreva-lence is higher in HIV-positive homo-sexual men than in HIV-positive pa-tients with hemophilia (13), just asacquired immunodeficiency syndrome(AIDS)-related KS occurs far morecommonly in homosexual men than inpatients with hemophilia. HHV-8 infec-tion is common in the general popula-tion of Uganda, which has a high inci-dence of endemic KS (11,13,14).The classic form of KS affectsmainly elderly men in Mediterraneanand Eastern Europe (16). If HHV-8 isthe major etiologic agent in KS, a higherprevalence of antibodies against HHV-8would be expected in regions with anelevated incidence of KS. KS is preva-lent in Italy, especially in the South,Sardinia, and the lower Po valley(Northern Italy) (16–18). From 1976through 1984, before the era of AIDS,elevated incidence rates of KS werefound in nine Italian cancer registries;these incidence rates were twofold tothreefold higher than those in the UnitedStates and Sweden and 10-fold higherthan those in the U.K. (17–20) (Fig. 1,A, and data not shown).We investigated the prevalence of an-tibodies against the HHV-8 latentnuclear antigen (LNA-1) by use of animmunofluorescence assay (13) in 747blood donors from different regions ofItaly. Since HHV-8 is also associatedwith primary effusion lymphoma (21)and multicentric Castleman’s disease(22), we additionally investigated the se-roprevalence of this lymphotropic her-pesvirus in 163 lymphoma patientsfrom the same Italian regions; 78 ofthese patients had Hodgkin’s disease,and 85 had non-Hodgkin’s lymphomas(64 of B-cell origin and 21 of T-cell ori-gin). The immunofluorescence assay isthe most sensitive and specific assaycurrently available to detect HHV-8 in-fection (23). Sera were tested in ablinded manner at a dilution of 1:100,and 38 positive sera were also titrated to
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