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

Abstract

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 < or = .0001) and high KSHV lytic (>1:1745; P < or = .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 < or =.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/microL; P = .004), including CD4-positive (+) cells (<457 cells/microL; P = .07) and CD8+ cells (<213cells/microL; P = .04), and with increased monocytes (> or =638 cells/microL; P = .009). Nonsignificant elevations of beta-2-microglobulin and neopterin were observed among cases regardless of disease burden (P > or = .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.

• Authors: Elizabeth E Brown, Denise Whitby, Francesco Vitale, Vickie Marshall, Georgina Mbisa, Christine Gamache, Carmela Lauria, Anthony J Alberg, Diego Serraino, Paola Cordiali-Fei, Angelo Messina, James J Goedert
• Journal: Cancer (Cancer) Vol. 107 Issue 9 Pg. 2282-90 (Nov 01 2006) ISSN: 0008-543X [Print] United States
• PMID: 16998933 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Disease Progression
• Female
• HIV Infections (complications, immunology)
• HIV-1 (immunology)
• Humans
• Italy
• Male
• Middle Aged
• Multivariate Analysis
• Risk Factors
• Sarcoma, Kaposi (complications, diagnosis, physiopathology)