经典型卡波西肉瘤的病毒学、血液学及免疫学危险因素

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

作者信息

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

机构信息

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.

出版信息

Cancer. 2006 Nov 1;107(9):2282-90. doi: 10.1002/cncr.22236.

DOI:10.1002/cncr.22236

PMID:16998933

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.

摘要

背景

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。

方法

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）。

结果

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。