Brown Elizabeth E, Whitby Denise, Vitale Francesco, Marshall Vickie, Mbisa Georgina, Gamache Christine, Lauria Carmela, Alberg Anthony J, Serraino Diego, Cordiali-Fei Paola, Messina Angelo, Goedert James J
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.
Cancer. 2006 Nov 1;107(9):2282-90. doi: 10.1002/cncr.22236.
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.
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.
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).
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.
经典型卡波西肉瘤（CKS）是一种炎症介导的肿瘤，在卡波西肉瘤相关疱疹病毒（KSHV）存在及免疫紊乱的情况下发生。在本研究中，作者将CKS病例与年龄和性别匹配的未感染人类免疫缺陷病毒1型且无病毒控制标志物、血细胞计数、CD4阳性和CD8阳性淋巴细胞以及血清β2微球蛋白和新蝶呤水平的KSHV血清阳性对照进行比较。
使用KSHV - K6和EBV - pol基因的实时扩增检测病毒载量，通过酶联免疫吸附测定检测抗K8.1（裂解）滴度，使用免疫荧光检测抗潜伏核抗原（LANA）滴度。使用经性别、年龄和研究地点调整的逻辑回归计算比值比（OR）和95%置信区间（95%CI）。
发现外周血单个核细胞（PBMC）KSHV DNA检测（P≤0.0001）以及高KSHV裂解（>1:1745；P≤0.0001）和潜伏（>1:102,400；P = 0.03）抗体滴度与CKS风险呈正相关。有病变的病例抗体滴度高于无病变的病例（P≤0.05）。未发现PBMC中爱泼斯坦 - 巴尔病毒（EBV）DNA检测与CKS相关（P = 0.95）。独立于PBMC KSHV DNA，发现CKS风险与血细胞比容降低（<37.4%；P = 0.03）、血红蛋白（<12g/dL；P = 0.04）和淋巴细胞（<1000个细胞/μL；P = 0.004）呈正相关，包括CD4阳性（+）细胞（<457个细胞/μL；P = 0.07）和CD8 +细胞（<213个细胞/μL；P = 0.04），以及与单核细胞增多（≥638个细胞/μL；P = 0.009）相关。无论疾病负担如何，病例中β2微球蛋白和新蝶呤均有非显著升高（P≥0.08）。在多变量模型中，发现CKS风险与PBMC KSHV DNA（OR为2.7；95%CI，1.4 - 5.3）、高KSHV裂解抗体滴度（OR为3.7；95%CI，1.9 - 7.4）以及低淋巴细胞，特别是年龄<70岁的患者（OR为8.0；95%CI，2.7 - 23.7）相关。
本研究结果似乎证实了KSHV的特异性，并突出了CKS发病机制中涉及的血液学和免疫学相关性。
