Characterization of humoral immune responses against p16, p53, HPV16 E6 and HPV16 E7 in patients with HPV-associated cancers
Characterization of humoral immune responses against p16, p53, HPV16 E6 and HPV16 E7 in patients with HPV-associated cancers
复制标题
DOI：
10.1002/ijc.23837
复制
发表时间：
2008-12-01
影响因子：
6.4
通讯作者：
Wentzensen, Nicolas
中科院分区：
文献类型：
--
作者：
Reuschenbach, Miriam;Waterboer, Tim;Wentzensen, Nicolas
细胞肿瘤抑制因子p16在宫颈癌和癌前病变中强烈过表达。我们之前已经证明，浸润性T淋巴细胞对p16的反应可以在宫颈癌患者中发现。在这里，我们分析了16是否诱导体液免疫反应。包括宫颈癌、口咽癌、结直肠癌和自身免疫性疾病患者的血清。共分析919份血清。包括486份来自宫颈癌病例对照研究的匹配血清。用western blot和新开发的覆盖完整p16蛋白的肽ELISA分析p16抗体。此外，采用基于luminex的多重检测同时检测针对p16、p53、HPV16 E6和HPV16 E7的抗体。在所有实体中，仅观察到低p16抗体反应性。表位定位显示p16蛋白的2个优势表位区域。在宫颈癌病例对照研究中，p16抗体频率（OR = 0.9, 95% Cl = 0.6-1.3）和p-53抗体频率（OR = 0.6, 95% Cl = 0.3-1.2）在患者与健康对照组之间无显著差异。宫颈癌患者中HPV16癌蛋白E6和E7抗体的检出率高于健康对照组（E6 OR = 27.8; 95% Cl = 11）。- 69.7， e7或= 5.7；95% Cl = 2.9-11.1)。在结论。尽管p16的强烈表达和观察到的细胞免疫反应的诱导，但仅在非常低的水平上观察到针对p16的抗体反应性，这与疾病背景无关。(C) 2008 Wiley-Liss, Inc。
The cellular tumor suppressor p16 is strongly overexpressed in cervical cancers and precancers. We have previously demonstrated that infiltrating T lymphocytes reactive against p16 can be found in cervical cancer patients. Here, we analyzed whether 16 induces humoral immune responses. Sera of patients with cervical cancer, oropharyngeal cancer, colorectal cancer and autoimmune disease were included. A total of 919 sera were analyzed. including 486 matched sera from a cervical cancer case control study. p16 antibodies were analyzed in western blot and a newly developed peptide ELISA covering the complete p16 protein. In addition, a Luminex-based multiplex assay was used for simultaneous detection of antibodies directed against p16, p53, HPV16 E6 and HPV16 E7. In all entities, only low p16 antibody reactivity was observed. Epitope mapping revealed 2 predominant epitope regions of the p16 protein. No significant difference in p16 antibody frequency (OR = 0.9; 95% Cl = 0.6-1.3) and p-53 antibody frequency (OR = 0.6; 95% Cl = 0.3-1.2) was found between patients and healthy controls in the cervical cancer case control study. Antibodies against the HPV16 oncoproteins E6 and E7 were detected more frequently in cervical cancer patients when compared with healthy controls (E6 OR = 27.8; 95 % Cl = 11. - 69.7, E7 OR = 5.7; 95% Cl = 2.9-11.1). In conclusion. despite the strong expression of p16 and the observed induction of cellular immune responses, antibody reactivity against p16 was observed only at very low levels independent of the disease background. (C) 2008 Wiley-Liss, Inc.