Kong Xiang-Wei, Bu Guo-Long, Chen Hua, Huang Yu-Hua, Liu Zhiwei, Kang Yin-Feng, Li Yan-Cheng, Yu Xia, Wu Biao-Hua, Li Zi-Qian, Chen Xin-Chun, Xie Shang-Hang, Lin Dong-Feng, Li Tong, Yan Shu-Mei, Han Run-Kun, Huang Nan, Wang Qian-Yu, Li Yan, Zhang Ao, Zhong Qian, Huang Xiao-Ming, Ye Weimin, Ji Ming-Fang, Cai Yong-Lin, Cao Su-Mei, Zeng Mu-Sheng
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, Guangdong, China.
Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
J Clin Invest. 2024 Nov 26;135(4):e180216. doi: 10.1172/JCI180216.
BACKGROUNDEBV is associated with nasopharyngeal carcinoma (NPC), but the existence of a NPC protective antibody against EBV-associated antigens remains unclear.METHODSPatients with NPC and matched controls were identified from prospective cohorts comprising 75,481 participants in southern China. ELISA and conditional logistic regression were applied to assess the effects of gp42-IgG on NPC. The expression of HLA-II, the gp42 receptor, in nasopharyngeal atypical dysplasia and its effect on EBV infection of epithelial cells were evaluated.FINDINGSgp42-IgG titers were significantly lower in patients with NPC compared with controls across various follow-up years before NPC diagnosis (P < 0.05). Individuals in the highest quartile for gp42-IgG titers had a 71% NPC risk reduction compared with those in the lowest quartile (ORsQ4vsQ1= 0.29, 95% CIs = 0·15 to 0.55, P < 0.001). Each unit antibody titer increase was associated with a 34% lower risk of NPC (OR = 0.66, 95% CI = 0.54-0.81, Ptrend< 0.001). The protective effect of of gp42-IgG was observed in patients diagnosed 5 years or more, 1-5 years, and less than 1 year after blood collection (P < 0.05). HLA-II expression was detected in 13 of 27 specimens of nasopharyngeal atypical dysplasia, and its overexpression substantially promoted epithelial cell-origin EBV infection.CONCLUSIONElevated EBV gp42-IgG titers can reduce NPC risk, indicating that gp42 is a potential EBV prophylactic vaccine target.TRIAL REGISTRATIONNCT00941538, NCT02501980, ChiCTR2000028776, ChiCTR2100041628.FUNDINGNoncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0501003), National Natural Science Foundation of China (82030046, 82073625, 81860601, 82373655), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2019BT02Y198), and Central Financial Transfer Payment Projects of the Chinese Government, Cancer Research Grant of Zhongshan City.
背景
EB病毒（EBV）与鼻咽癌（NPC）相关，但针对EBV相关抗原的鼻咽癌保护性抗体是否存在仍不清楚。
方法
从中国南方75481名参与者的前瞻性队列中确定鼻咽癌患者和匹配的对照组。采用酶联免疫吸附测定（ELISA）和条件逻辑回归评估gp42-IgG对鼻咽癌的影响。评估鼻咽癌非典型增生中gp42受体HLA-II的表达及其对上皮细胞EBV感染的影响。
结果
在鼻咽癌诊断前的各个随访年份中，鼻咽癌患者的gp42-IgG滴度显著低于对照组（P < 0.05）。gp42-IgG滴度处于最高四分位数的个体与最低四分位数的个体相比，患鼻咽癌的风险降低了71%（ORQ4vsQ1 = 0.29，95%CI = 0.15至0.55，P < 0.001）。抗体滴度每增加一个单位，患鼻咽癌的风险降低34%（OR = 0.66，95%CI = 0.54 - 0.81，Ptrend < 0.001）。在采血后5年或更长时间、1 - 5年以及少于1年诊断出的患者中均观察到gp42-IgG的保护作用（P < 0.05）。在27份鼻咽癌非典型增生标本中的13份中检测到HLA-II表达，其过表达显著促进上皮细胞源性EBV感染。
结论
EBV gp42-IgG滴度升高可降低鼻咽癌风险，表明gp42是潜在的EBV预防性疫苗靶点。
试验注册
NCT00941538、NCT02501980、ChiCTR2000028776、ChiCTR2100041628。
资助
国家科技重大专项 - 非传染性慢性病（2023ZD0501003）、中国国家自然科学基金（82030046、82073625、81860601、82373655）、广东省珠江人才计划地方创新和研究团队项目（2019BT02Y198）以及中国政府中央财政转移支付项目、中山市癌症研究资助。
