Objective: To assess the diagnostic and prognostic value of lymphocyte subtyping for invasive candidiasis infection (ICI) in critically ill patients with non-neutropenic sepsis. Methods: A prospective observational cohort study was performed at Peking Union Medical College Hospital (PUMCH), 377 patients with non-neutropenic sepsis admitted to Department of Critical Care Medicine from January 2017 to November 2019 were enrolled. There were 9.0% (34/377) patients diagnosed as ICI. Vital signs, supportive care therapy and microbiological specimens were collected. Peripheral blood lymphocyte subtypes, serum globulin, complements, inflammatory factors such as interleukin(IL)-6, IL-8, IL-10 and tumor necrosis factor were detected within 24 hours after sepsis was diagnosed. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value and prognostic significance of immunological indicators for ICI. Multiple logistic regression was used to analyze the independent risk factors for ICI. Kaplan-Meier analysis was used to analyze survival. Results: The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was 17.0 (13.0, 21.0) in all 377 patients. The sequential organ failure score (SOFA) was 11.0 (8.0, 13.0), and the 28-day mortality rate was 27.6% (104/377). Peripheral blood CD8+absolute T lymphocyte count≤177 cells/μl, CD28+CD8+T-cell count≤81 cells/μl and 1, 3-β-D-glucan (BDG) ≥88.20 ng/L were closely correlated with the diagnosis of ICI (AUC=0.793,95%CI 0.749-0.833,P<0.000 1;AUC=0.892,95%CI 0.856-0.921, P<0.000 1;AUC=0.761, 95%CI 0.715-0.803,P<0.000 1, respectively), with sensitivity of diagnosis 94.12%, 100.00%, and 88.24%; the specificity of diagnosis 81.34%, 62.39%, 63.56% respectively. Multivariate logistic regression analysis identified CD8+T-cell count≤139 cells/μl (OR=7.463, 95%CI 1.300-42.831, P=0.024) and CD28+CD8+T-cell counts≤52 cells/μl (OR=57.494, 95%CI 3.986-829.359, P=0.003) as independent risk factors for higher mortality. Kaplan-Meier survival analysis suggested that CD8+T-cell count ≤139 cells/μl (P=0.0159) and CD28+CD8+T-cell count≤52 cells/μl (P=0.000 1) were associated with higher mortality within 28 days (68.8%, 91.7%). Conclusions: Low CD28+CD8+T cell count in peripheral blood is closely related to the development and clinical outcome of ICI in sepsis patients, which could be used as an effective indicator for the diagnosis and prognosis prediction of ICI.
目的： 探讨T细胞亚群对非粒细胞缺乏重症脓毒症患者侵袭性念珠菌感染（ICI）的诊断意义及预后价值。 方法： 前瞻性、观察性队列研究。选2017年1月至2019年11月北京协和医院重症医学科收治非粒细胞缺乏重症脓毒症患者377例，其中ICI患者34例，非ICI患者343例。脓毒症诊断24 h内取血检测CD8+T细胞、 CD28+CD8+T细胞等细胞比例，测血IgA、IgM、IgG、补体C3、补体C4及白细胞介素（IL）-6、IL-8、IL-10、肿瘤坏死因子（TNF）α水平。受试者操作特征（ROC）曲线评估免疫学指标对ICI诊断的意义及预后价值。采用多元logistic回归分析ICI诊断的独立危险因素。通过Kaplan-Meier生存分析绘制生存曲线。 结果： 377例患者急性生理与慢性健康状况评分Ⅱ（APACHEⅡ）17.0（13.0， 21.0）分，序贯器官衰竭评分（SOFA）11.0（8.0， 13.0）分，28 d病死率27.6%（104/377）。CD8+T细胞计数≤177个/μl、CD28+CD8+T细胞计数≤81个/μl、G试验≥88.20 ng/L与ICI诊断密切相关［曲线下面积（AUC）0.793，95%CI 0.749~0.833，P<0.000 1；AUC 0.892，95%CI 0.856~0.921， P<0.000 1；AUC 0.761， 95%CI 0.715~0.803，P<0.000 1］。CD28+CD8+T细胞计数诊断ICI的敏感度为94.12%，特异度为81.34%；CD8+T细胞计数敏感度为100.00%，特异度为62.39%；G试验敏感度为88.24%，特异度为63.56%。多元logistic回归分析显示，CD8+T细胞计数≤139个/μl（OR=7.463，95%CI 1.300~42.831，P=0.024）和CD28+CD8+T细胞计数≤52个/μl（OR=57.494，95%CI 3.986~829.359，P=0.003）是影响ICI患者预后的独立危险因素。Kaplan-Meier生存曲线显示，CD8+T细胞计数≤139个/μl（P=0.015 9）或CD28+CD8+T细胞计数≤52个/μl（P=0.000 1）的ICI患者28 d病死率更高（11/16，11/12）。 结论： CD28+CD8+T细胞计数在非粒细胞缺乏重症脓毒症患者ICI早期显著降低，与ICI诊断和预后密切相关，具有临床检测价值。.
Keywords: Invasive candidiasis infection; Lymphocyte subtyping; Sepsis.