【摘要】 目的 探讨老年肺炎患者的抗菌抗体和T细胞反应与肺细菌定植和肺功能的关系。方法 回顾性选择2019年6月至2021年4月在南京医科大学第一附属医院老年科因肺炎住院治疗的73例老年患者作为老年肺炎组，30名同期无肺炎或肺部感染等疾病的健康体检人员作为对照组。根据电子档案记录对参与人员的一般资料进行统计。使用酶联免疫吸附试验方法检测血清细菌抗体水平。通过ELIspot测量T细胞微生物抗原的反应。使用流式细胞术分析细菌抗原刺激产生的CD4~+CD69~+T细胞比率。通过肺活量测定以确定1 s内用力呼气量(FEV1)和用力肺活量(FVC)，计算FEV1%预测值。分析T细胞反应和肺功能FEV1%的相关性。结果 (1)老年肺炎组抗铜绿假单胞菌抗体、抗流感嗜血杆菌抗体和抗嗜麦芽窄食单胞菌抗体水平较对照组升高，抗肺炎链球菌抗体较对照组降低，差异均有统计学意义(P <0.05)。(2)老年肺炎组对铜绿假单胞菌、流感嗜血杆菌、肺炎链球菌和嗜麦芽窄食单胞菌刺激产生的γ干扰素(IFNγ)斑点形成细胞数量较对照组减少，差异均有统计学意义(P <0.05)。(3)不同抗原刺激下老年肺炎组与对照组活化CD4~+CD69~+T细胞比较差异无统计学意义(P> 0.05),2种细菌抗原刺激后两组PBMC中CD4~+CD69~+T细胞比率均显著高于未刺激PBMC，流感嗜血杆菌刺激后该比率也显著高于铜绿假单胞菌刺激差异均有统计学意义(P<0.05)。(4)细菌当前定植患者较无定植、偶尔定植和以前定植的患者肺功能指标FEV1%显著降低，差异均有统计学意义(P <0.05)，而当细菌定植变得更加频繁且当前培养呈阳性时，老年患者的肺功能呈显著下降趋势。(5) T细胞反应和肺功能FEV1%呈正相关(r=0.501,P=0.033)。结论 肺炎老年患者肺细菌定值会产生抗体反应，其抗体反应水平与暴露水平、肺功能降低的水平呈正比;另外，T细胞反应在感染率增加的患者中降低，并且与流感嗜血杆菌的肺功能呈正比，因此推测其均可能与肺炎患者疾病进展或肺功能改善密切相关。更多还原

【Abstract】 Objective To investigate the relationship between antibacterial antibodies and T cell responses in elderly patients with pneumonia and lung bacterial colonization and lung function. Methods A retrospective selection of 73 elderly patients who were hospitalized for pneumonia in the Department of Geriatrics,the First Affiliated Hospital of Nanjing Medical University from June 2019 to April 2021 were included in the elderly pneumonia group. Thirty health examiners who had no pneumonia or lung infection during the same period served as the control group.The general information of the participants shall be counted according to the electronic file records. The serum bacterial antibody levels were detected by using an enzyme-linked immunosorbent assay method. T cell microbial antigen responses were measured by ELIspot. The proportion of CD4~+CD69~+T cells generated by bacterial antigen stimulation was analyzed by flow cytometry. FEV1% predicted value was calculated by spirometry to determine forced expiratory volume in 1 second( FEV1) and forced vital capacity( FVC). The correlation between T cell response and pulmonary function FEV1% was analyzed. Results( 1) The levels of anti-Pseudomonas aeruginosa antibody,anti-Haemophilus influenzae antibody and anti-Stenotrophomonas maltophilia antibody in the elderly pneumonia group were higher than those in the control group,and the anti-Streptococcus pneumoniae antibody in the elderly pneumonia group was lower than that in the control group,the differences were statistically significant( P < 0. 05).( 2) The number of gamma interferon( IFNγ) spot-forming cells stimulated by Pseudomonas aeruginosa,Haemophilus influenzae,Streptococcus pneumoniae and Stenotrophomonas maltophilia in the aged pneumonia group was lower than that in the control group,the differences were statistically significant( P < 0. 05).( 3) There was no difference in activated CD4~+CD69~+T cells between the aged pneumonia group and the control group under different antigen stimulation( P > 0. 05). The proportion of CD4~+CD69~+T cells in PBMCs f two groups after stimulated by the two bacterial antigens was significantly higher than that in unstimulated PBMCs,and the ratio was also significantly higher after stimulation with Haemophilus influenzae than with stimulation with Pseudomonas aeruginosa,the differences were statistically significant( P< 0. 05).( 4) Compared with the patients without colonization,occasional colonization and previous colonization,the FEV1% of the lung function index in patients with current bacterial colonization was significantly lower,the differences were statistically significant( P < 0. 05),however,when bacterial colonization became more frequent and the current culture was positive,lung function in elderly patients showed a significant downward trend( P < 0. 05).( 5) There was a positive correlation between T cell response and pulmonary function FEV1%( r = 0. 501,P = 0. 033).Conclusion Lung bacterial determination in elderly patients with pneumonia will produce antibody responses,and the level of antibody responses is proportional to the exposure level and the level of reduced lung function. In addition,T cell responses were decreased in patients with increased infection rates and were proportional to H. influenzae lung function,so it is speculated that both may be closely related to disease progression or improvement in lung function in patients with pneumonia.更多还原