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RESEARCH PRODUCT

Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma.

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BACKGROUND Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm that develops in the presence of KS-associated herpesvirus (KSHV) and immune perturbation. In the current study, the authors compared CKS cases with age-matched and sex-matched KSHV-seropositive controls without human immunodeficiency virus-1 infection and markers of viral control, blood counts, CD4-positive and CD8-positive lymphocytes, and serum β-2-microglobulin and neopterin levels. METHODS Viral loads were detected using real-time amplification of the KSHV-K6 and EBV-pol genes, anti-K8.1 (lytic) titers were detected by enzyme-linked immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detected using immunofluorescence. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression adjusted for sex, age, and study site. RESULTS Peripheral blood mononuclear cells (PBMC) KSHV DNA detection (P ≤ .0001) and high KSHV lytic (>1:1745; P ≤ .0001) and latent (>1:102,400; P = .03) antibody titers were found to be positively associated with CKS risk. Antibody titers were higher in cases with lesions compared with cases without lesions (P ≤.05). The detection of Epstein-Barr virus (EBV) DNA in PBMCs was not found to be associated with CKS (P = .95). Independent of PBMC KSHV DNA, CKS risk was found to be positively associated with reduced hematocrit (<37.4%; P = .03), hemoglobin (<12g/dL; P = .04), and lymphocytes (<1000 cells/μL; P = .004), including CD4-positive (+) cells (<457 cells/μL; P = .07) and CD8+ cells (<213cells/μL; P = .04), and with increased monocytes (≥638 cells/μL; P = .009). Nonsignificant elevations of β-2-microglobulin and neopterin were observed among cases regardless of disease burden (P ≥ .08). In a multivariate model, the CKS risk was found to be associated with PBMC KSHV DNA (OR of 2.7; 95% CI, 1.4–5.3), a high KSHV lytic antibody titer (OR of 3.7; 95% CI, 1.9–7.4), and low lymphocytes, particularly among those patients age <70 years (OR of 8.0; 95% CI, 2.7–23.7). CONCLUSIONS The findings of the current study appear to corroborate the specificity of KSHV and highlight the hematologic and immunologic correlates involved in the pathogenesis of CKS. Cancer 2006. Published 2006 by the American Cancer Society.