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 < 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.
Brown
Elizabeth E
EE
Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA. elbrown@uab.edu
Whitby
Denise
D
Vitale
Francesco
F
Marshall
Vickie
V
Mbisa
Georgina
G
Gamache
Christine
C
Lauria
Carmela
C
Alberg
Anthony J
AJ
Serraino
Diego
D
Cordiali-Fei
Paola
P
Messina
Angelo
A
Goedert
James J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D012514:Sarcoma, Kaposi / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology*
D015415:Biomarkers