HIV阴性肺结核患者外周血CD4+T淋巴细胞减少的免疫干预意义及影响因素分析

目的: 探讨HIV阴性肺结核患者外周血CD4⁺T淋巴细胞减少的发生率、免疫干预意义和影响因素。 方法: 回顾性分析2020年12月至2021年7月安徽省胸科医院收治的213例肺结核患者,根据外周血CD4⁺T淋巴细胞计数分为CD4⁺T淋巴细胞减少组(计数<410个/μl)和对照组(计数≥410个/μl);将CD4⁺T淋巴细胞减少患者根据是否行免疫干预治疗分为免疫干预组和非免疫干预组。收集研究对象的人口学特征(性别、年龄、职业、文化水平)、吸烟、饮酒、症状数目、治疗分类、合并疾病、耐药情况、影像学及实验室检查结果等临床资料。疗效分析组间比较采用χ²检验。经单因素分析筛选后,采用多因素logistic回归分析探讨HIV阴性肺结核患者外周血CD4⁺T淋巴细胞减少的影响因素。 结果: 213例肺结核患者中,61例发生CD4⁺T淋巴细胞减少,发生率为28.6%。疗效分析显示治疗2~4个月,免疫干预组痰涂片阴性率为93.9%,高于非免疫干预组的75.0%(χ²=4.320,P<0.05)。治疗5~7个月,免疫干预组病灶吸收率为51.5%,高于非免疫干预组的25.0%(χ²=4.462,P<0.05)。单因素分析显示,CD4⁺T淋巴细胞减少组男性、年龄≥60岁、农民职业、文盲文化、症状数目≥4个、并发肺外结核、累及肺野4~6个、肺部空洞、血红蛋白<110g/L、血小板<125×10⁹/L、白蛋白<35g/L、CD8⁺T淋巴细胞计数<190个/μl的构成比(77.0%、44.3%、36.1%、26.2%、36.1%、34.4%、77.0%、55.7%、45.9%、18.0%、68.9%、29.5%)均明显高于对照组(60.5%、11.2%、19.7%、10.5%、19.7%、21.1%、38.2%、40.8%、25.7%、5.3%、44.7%、7.9%),差异均有统计学意义(χ²值分别为5.242、29.060、10.095、13.650、6.290、4.165、26.342、3.929、8.274、8.738、10.137、16.805,P值均<0.05)。多因素logistic回归分析显示,肺结核患者CD4⁺T淋巴细胞减少的危险因素有:年龄≥60岁(OR=4.816,95%CI:1.650~14.052)、病变累及肺野4~6个(OR=3.669,95%CI:1.548~8.696)、血小板<125×10⁹/L(OR=3.753,95%CI:1.069~13.173)、CD8⁺T淋巴细胞计数<190个/μl(OR=3.908,95%CI:1.394~10.954)。 结论: HIV阴性肺结核患者较易发生CD4⁺T淋巴细胞减少,免疫干预治疗对提高患者疗效具有积极意义。高龄、肺部病变累及范围大、血小板减少和CD8⁺T淋巴细胞减少是肺结核患者CD4⁺T淋巴细胞减少的独立危险因素。

Study on the significance of immune intervention and influencing factors of peripheral blood CD4+T lymphocytopenia in HIV-negative pulmonary tuberculosis patients

Objective: To investigate the incidence, immune intervention value, and influencing factors of peripheral blood CD4⁺T lymphocytopenia in HIV-negative pulmonary tuberculosis (PTB) patients. Methods: The clinical data of 213 cases with HIV-negative PTB in Anhui Chest Hospital from December 2020 to July 2021 were analyzed, retrospectively. According to the CD4⁺T lymphocytes counts, 213 cases were divided into CD4⁺T lymphopenia group (count <410 cells/μl) and control group (count ≥410 cells/μl). The patients with CD4⁺T lymphopenia were divided into the immune intervention group and non-intervention group according to whether they received immune intervention. Demographic characteristics (gender, age, occupation, and education level), smoking, drinking, number of symptoms, treatment classifications, comorbid diseases, drug resistance, imaging, and laboratory test results were collected. Efficacy analysis between groups was compared using the Chi-square test. Multivariate logistic regression analysis was used after filtrating by univariate analysis to explore the influencing factors of peripheral blood CD4⁺T lymphocytopenia in HIV-negative PTB patients. Results: The incidence of CD4⁺T lymphopenia was 28.6% (61/213). The efficacy analysis showed that after 2-4 months of treatment, the negative rate of sputum smear in the immunological intervention group was 93.9%, higher than 75.0% in the non-intervention group (χ²=4.320, P<0.05). After 5-7 months of treatment, the absorption rate of lesions in the immunological intervention group was 51.5%, which was higher than 25.0% in the non-intervention group (χ²=4.462,P<0.05). Univariate analysis showed that in the CD4⁺T lymphopenia group, male, age ≥60 years, farming, illiterate culture, number of symptoms ≥4, complicated with extrapulmonary tuberculosis, involving 4-6 lung fields, pulmonary cavity, hemoglobin <110 g/L, platelet <125×10⁹/L, albumin <35 g/L, CD8⁺T lymphocyte count <190/μl (77.0%, 44.3%, 36.1%, 26.2%, 36.1%, 34.4%, 77.0%, 55.7%, 45.9%, 18.0%, 68.9%, 29.5%) were significantly higher than that of control group (60.5%, 11.2%, 19.7%, 10.5%, 19.7%, 21.1%, 38.2%, 40.8%, 25.7%, 5.3%, 44.7%, 7.9%), the differences were statistically significant (χ² values were 5.242, 29.060, 10.095, 13.650, 6.290, 4.165, 26.342, 3.929, 8.274, 8.738, 10.137, and 16.805, respectively, all P values <0.05). Multivariate logistic regression analysis showed that age ≥60 years old, lesion involvement of 4-6 lung fields, platelet <125×10⁹/L, CD8⁺T lymphocytes count <190 cells/μl (OR=4.816,95%CI:1.650-14.052; OR=3.669,95%CI:1.548-8.696; OR=3.753,95%CI:1.069-13.173; OR=3.908,95%CI:1.394-10.954) were the risk factors of CD4⁺T lymphocytopenia. Conclusion: HIV-negative pulmonary tuberculosis patients were prone to a decrease in CD4⁺T lymphocytes, and immune intervention therapy had positive significance for improving the efficacy of this population. Old age, a wide range of lesions involved, thrombocytopenia, and CD8⁺T lymphocytopenia were the independent risk factors for CD4⁺T lymphocytopenia in HIV-negative PTB patients.