Antibodies to Butyrate-Inducible Antigens of Kaposi's SarcomaAssociated Herpesvirus in Patients with HIV-1 Infection
George Miller, M.D., Michael O. Rigsby, M.D., Lee Heston, M.S., Elizabeth Grogan, B.S., Ren Sun, Ph.D., Craig Metroka, M.D., Ph.D., Jay A. Levy, M.D., Shou-Jiang Gao, Ph.D., Yuan Chang, M.D., and Patrick Moore, M.D., M.P.H.
Background The recent identification in patients with Kaposi'ssarcoma of DNA sequences with homology to gammaherpesviruseshas led to the hypothesis that a newly identified virus, Kaposi'ssarcomaassociated herpeslike virus (KSHV), has a rolein the pathogenesis of Kaposi's sarcoma. We developed serologicmarkers for KSHV infection.
Methods KSHV antigens were prepared from a cell line (BC-1)that contains the genomes of both KSHV and the EpsteinBarrvirus (EBV). We used immunoblot and immunofluorescence assaysto examine serum samples from 102 patients with human immunodeficiencyvirus type 1 (HIV-1) infection for antibodies to KSHV-associatedproteins and to distinguish these antibodies from antibodiesto EBV antigens. A positive serologic response was defined bythe recognition of an antigenic polypeptide, p40, in n-butyratetreatedBC-1 cells and by the absence of p40 recognition in untreatedBC-1 cells or EBV-infected, KSHV-negative cells. The detectionby the immunofluorescence assay of 10 to 20 times more antigen-positivecells in n-butyratetreated BC-1 cells than in untreatedcells was considered a positive response.
Results Antibodies to the p40 antigen expressed by chemicallytreated BC-1 cells were identified in 32 of 48 HIV-1infectedpatients with Kaposi's sarcoma (67 percent), as compared withonly 7 of 54 HIV-1infected patients without Kaposi'ssarcoma (13 percent). These results were confirmed by an immunofluorescenceassay. The positive predictive value of the serologic testsfor Kaposi's sarcoma was 82 percent, and the negative predictivevalue 75 percent.
Conclusions The presence of antibodies to a KSHV antigenic peptidecorrelates with the presence of Kaposi's sarcoma in a high-riskpopulation and provides further evidence of an etiologic rolefor KSHV.
Source Information
From the Departments of Pediatrics (G.M., L.H., E.G.), Internal Medicine (M.O.R.), Epidemiology and Public Health (G.M.), Molecular Biophysics and Biochemistry (G.M., R.S.), and Genetics (R.S.), Yale University School of Medicine, New Haven, Conn.; St. Luke'sRoosevelt Hospital Center, New York (C.M.); the University of California, San Francisco, School of Medicine, San Francisco (J.A.L.); and the College of Physicians and Surgeons and School of Public Health, Columbia University, New York (C.M., S.-J.G., Y.C., P.M.).
Address reprint requests to Dr. Miller at the Department of Pediatrics, Yale University School of Medicine, 333 Cedar St., Rm. 420 LSOG, New Haven, CT 06520.
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