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

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 beta-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/mu L; P = .004), including CD4-positive (+) cells (< 457 cells/mu L; P = .07) and CD8+ cells (< 213cells/mu L; P = .04), and with increased monocytes (>= 638 cells/mu L; P = .009). Nonsignificant elevations of beta-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.

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