微生物与感染
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微生物与感染  2022, Vol. 17 Issue (6): 347-359    DOI: 10.3969/j.issn.1673-6184.2022.06.002
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慢性乙型肝炎患者外周血循环免疫复合物的临床意义探索
唐怡洁1,邬敏1,陆伟1,冯艳玲1,袁正宏2,张小楠1, 3,张占卿1
1. 复旦大学附属上海市公共卫生临床中心,上海 201508; 2. 复旦大学上海医学院基础医学院教育部/卫健委/中国医科院医学分子病毒学重点实验室,上海 200032; 3. 堪培拉大学,澳大利亚首都直辖区 2617,澳大利亚
Clinical significance of circulating immune complexes in patients with chronic hepatitis B
TANG Yijie1, WU Min1, LU Wei1, FENG Yanling1, YUAN Zhenghong2, ZHANG Xiaonan1,3, ZHANG Zhanqing1
1. Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; 2. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; 3. University of Canberra, Australia Capital Territory 2617, Australia
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摘要: 免疫复合物的形成是病毒在感染过程中造成机体损伤的重要原因之一。对病毒感染者进行免疫复合物的定量有助于监测疾病进展,了解病毒与宿主之间的相互作用。本研究对早期固相C1q结合荧光免疫法进行优化,并利用补体分子C1q特异性结合慢性乙型肝炎(chronic hepatitis B,CHB)患者血液中的循环免疫复合物(circulating immune complex,CIC),通过荧光标记的羊抗人IgG对CIC进行检测。针对220例CHB患者、20例非乙型肝炎的肝炎患者、20例健康者、10例CHB功能性治愈者,分析了CHB患者中的CIC水平及其与CHB诊断所用病毒学指标、肝功能生化指标之间的关系。结果显示:约97%的CHB患者存在CIC水平升高,且与病毒学指标乙型肝炎病毒表面抗原(hepatitis B virus surface antigen,HBsAg)(r=0.197 3,P=0.005 8)、HBV DNA(r=0.217 8,P=0.002 3)显著正相关;与肝脏损伤相关生化指标丙氨酸转氨酶(alanine aminotransferase,ALT)(r=0.158 0,P=0.020 0)、天冬氨酸转氨酶(aspartate aminotransferase,AST)(r=0.151 3,P=0.035 3)呈正相关,而与补体C4(r=-0.21,P=0.003)呈负相关。不同程度的炎症和纤维化患者之间CIC和补体水平有显著性差异,且随临床分期产生相应波动。在免疫耐受期和低复制期,患者CIC水平较低而补体水平升高;在免疫激活期和HBV e抗原(HBV e antigen,HBeAg)阴性肝炎患者中的结果则相反。结果提示,CHB患者血液循环中存在CIC生成所造成的肝脏损伤及补体大量消耗,对CIC进行监测能在一定程度上反映CHB患者潜在的肝损伤。
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唐怡洁1
邬敏1
陆伟1
冯艳玲1
袁正宏2
张小楠1
3
张占卿1
关键词 乙型肝炎病毒免疫复合物补体肝脏炎症    
Abstract:The formation of immune complexes is considered to be one of the important causes of inflammatory injury during virus infection. Quantification of immune complexes in virus-infected patients can help monitor disease progression and understand virus-host interactions. In this study, a solid-phase C1q-binding fluorescence immunoassay method quantifying circulating immune complexes (CICs) based on published reports was optimized. Using complement molecule C1q for capturing the immune complexes, and fluorescent-labeled goat anti-human IgG for readout, the clinical significance of CICs in 220 chronic hepatitis B (CHB) patients, 20 non-hepatitisB virus (HBV) hepatitis patients, 20 healthy controls, and 10 individuals recovered from CHB were explored. The results showed that about 97% of CHB patients had elevated CIC levels, which were significantly positively correlated with virological indicators HBV surface antigen (HBsAg) (r=0.197 3, P=0.005 8) and HBV DNA (r=0.217 8,P=0.002 3). More importantly, CIC levels were positively correlated with liver injury-related biochemical indicators alanine aminotransferase (ALT) (r=0.158 0, P=0.020 0) and aspartate aminotransferase (AST) (r=0.151 3, P=0.035 3), while was negatively correlated with complement C4 (r=-0.210 0, P=0.003 0). The levels of CICs and complements showed significant differences among the patients with different levels of inflammation and fibrosis, and their levels fluctuated correspondingly with clinical stages of CHB. Among the patients in immune tolerance and low replication stages, the content of CICs was lower and the serum complement level was elevated. But, the results were the opposite among the patients in immune active stage and HBV e antigen (HBeAg)-negative hepatitis. The above results all suggest that there are liver damage and a large consumption of complements caused by the formation of CICs in the blood circulation of CHB patients. The monitoring of CICs can reflect the potential damage of CHB patients to a certain extent.
Key wordsHepatitis B virus    Circulating immune complex    Complement    Liver inflammation
:  R373.2  
基金资助:国家自然科学基金项目(32070152,81873962)
通讯作者: 张占卿,袁正宏,张小楠   
引用本文:   
唐怡洁1,邬敏1,陆伟1,冯艳玲1,袁正宏2,张小楠1, 3,张占卿1. 慢性乙型肝炎患者外周血循环免疫复合物的临床意义探索[J]. 微生物与感染, 2022, 17(6): 347-359.
TANG Yijie1, WU Min1, LU Wei1, FENG Yanling1, YUAN Zhenghong2, ZHANG Xiaonan1,3, ZHANG Zhanqing1. Clinical significance of circulating immune complexes in patients with chronic hepatitis B. JOURNAL OF MICROBES AND INFECTIONS, 2022, 17(6): 347-359.
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http://jmi.fudan.edu.cn/CN/10.3969/j.issn.1673-6184.2022.06.002     或     http://jmi.fudan.edu.cn/CN/Y2022/V17/I6/347

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