发热伴血小板减少综合征与恙虫病患者免疫损伤的差异比较  

Differences in immune damage between patients with severe fever with thrombocytopenia syndrome and patients with tsutsugamushi disease

作　　者：胡立芬[1] 孔钦翔 岳程程 贺玲玲 夏玲玲[1] 李家斌[1,2] Hu Lifen;Kong Qinxiang;Yue Chengcheng;He Lingling;Xia Lingling;Li Jiabin(Department of Infectious Diseases,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui,China;Department of Infectious Diseases,Chaohu Hospital of Anhui Medical University,Hefei 230022,Anhui,China)

机构地区：[1]安徽医科大学第一附属医院感染科,合肥230022 [2]安徽医科大学附属巢湖医院感染科,合肥230022

出　　处：《中华危重病急救医学》2020年第8期947-952,共6页Chinese Critical Care Medicine

基　　金：国家自然科学基金(81101313);国家科技重大专项(2017ZX10204401);安徽省"十二五"临床重点专科建设项目(2013-228);安徽省临床重点专科建设项目(2017-529)。

摘　　要：目的比较发热伴血小板减少综合征(SFTS)与恙虫病两种疾病患者病程中免疫损伤的差异.方法采用前瞻性病例对照研究,选择2014年10月至2017年6月安徽医科大学第一附属医院收治的31例SFTS患者和16例恙虫病患者,另外以10例健康体检者作为对照.用流式细胞仪检测患者外周血CD4+、CD8+T淋巴细胞计数以及CD3+T淋巴细胞、自然杀伤细胞(NK细胞)、B淋巴细胞及浆细胞的比例;同时用Luminex液相芯片平台技术检测外周血34个细胞因子水平.比较两组患者间淋巴细胞及细胞因子的差异.结果SFTS患者外周血CD3+T淋巴细胞比例、CD4+及CD8+T淋巴细胞计数明显低于恙虫病患者(t值分别为4.860、9.411和5.030,均P<0.01),NK细胞及B淋巴细胞比例明显高于恙虫病患者(t值分别为2.344和5.896,均P<0.05).SFTS患者病程中外周血浆细胞比例为(7.7±1.2)%,危重患者最高可达30%,都表现为λ单克隆型细胞群;而恙虫病患者外周血中未检测到浆细胞.检测34个细胞因子水平发现,SFTS与恙虫病患者白细胞介素-1受体抗体(IL-1RA)、白细胞介素(IL-6、IL-15、IL-10、IL-8)、肿瘤坏死因子-α(TNF-α)、γ-干扰素(IFN-γ)、粒细胞集落刺激因子(G-CSF)、嗜酸粒细胞趋化因子(Eotaxin)、IFN-γ诱导蛋白10(IP-10)、单核细胞趋化蛋白1(MCP-1)、巨噬细胞炎症蛋白(MIP-1α、MIP-1β)、血小板源生长因子(PDGF-AA、PDGF-AB/BB)及受激活调节正常T细胞表达和分泌因子(RANTES)表达均异常,其中SFTS患者IL-1RA、IL-6、IL-15、IL-10、TNF-α、IFN-γ、G-CSF、Eotaxin、IL-8、IP-10、MCP-1和MIP-1α水平明显高于恙虫病患者(Z值分别为2.312、2.447、3.660、5.444、1.965、2.402、2.402、2.997、3.525、2.481、3.817和2.211,均P<0.05),PDGF-AA、PDGF-AB/BB和RANTES分泌水平明显低于恙虫病患者(Z值分别为3.728、2.514和2.649,均P<0.05).相关性分析发现,RANTES、PDGF-AA和PDGF-AB/BB水平均与SFTS、恙虫病患者血小板水平呈明显正相关(SFTS:rObjective To analyze the difference of immune damage between patients with severe fever with thrombocytopenia syndrome(SFTS)and patients with tsutsugamushi disease.Methods A prospective case-control study was conducted.Thirty-one patients with SFTS and 16 patients with tsutsugamushi disease admitted to the First Affiliated Hospital of Anhui Medical University from October 2014 to June 2017 were enrolled,and another 10 healthy people were enrolled as control.The counts of CD4+and CD8+T lymphocytes,and the proportion of CD3+T lymphocytes,natural kill cells(NK cells),B lymphocytes and plasma cells were detected by flow cytometry.Thirty-four inflammatory mediators were determined by a multiplex Luminex®system synchronously.The differences of lymphocytes and cytokines between the two groups were compared.Results The proportion of CD3+T lymphocytes,the counts of CD4+and CD8+T lymphocytes in SFTS patients were significantly lower than those in patients with tsutsugamushi disease(t values were 4.860,9.411 and 5.030,respectively,all P<0.01),and the proportion of NK cells and B lymphocytes were significantly higher than those in patients with tsutsugamushi disease(t values were 2.344 and 5.896,respectively,both P<0.05).The proportion of plasma cells in peripheral blood of SFTS patients was(7.7±1.2)%,the highest proportion of plasma cells in severe SFTS patients was up to 30%,and all patients showedλmonoclonal cell group in plasma cells.No plasma cells were detected in tsutsugamushi disease patients.The abnormal expressions of interleukin-1 receptor antibody(IL-1RA),interleukin(IL-6,IL-15,IL-10,IL-8),tumor necrosis factor-α(TNF-α),γ-interferon(IFN-γ),granulocyte colony-stimulating factor(G-CSF),eosinophil chemotactic factor(Eotaxin),IFN-γ-inducible protein-10(IP-10),monocyte chemoattractant protein-1(MCP-1),macrophage inflammatory protein(MIP-1α,MIP-1β),platelet-derived growth factor(PDGF-AA,PDGF-AB/BB),activated regulatory normal T cells and secretion factors(RANTES)were found in patients with SFTS and tsutsugamu

关 键 词：发热伴血小板减少综合征 恙虫病 淋巴细胞 免疫损伤 

分 类 号：R512.8[医药卫生—内科学] R513.2[医药卫生—临床医学]