Value of cytometry microsphere array technology in differential diagnosis of infection status and types in patients with multiple myeloma
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摘要: 目的 探析流式微球阵列技术(cytometric bead array，CBA)鉴别诊断多发性骨髓瘤(multiple myeloma，MM)患者感染状态及类型的价值。方法 采用回顾性队列研究方法，收集2019年1月—2022年12月医院收治的214例MM患者临床资料，按照是否感染分为MM合并感染患者作为观察组(110例)，MM未感染患者作为对照组(104例)。110例感染观察组中，49例为革兰阳性菌感染(G+菌感染组)，48例为革兰阴性菌感染(G-菌感染组)，13例为真菌感染。所有样本采用CBA检测技术检测Th1/Th2细胞因子谱。比较辅助性T细胞(Th)1/Th2细胞因子谱、C-反应蛋白(CRP)和降钙素原(PCT)水平，观察MM患者未感染及感染状态下Th1/Th2细胞因子谱特征，分析CBA检测技术检测Th1/Th2细胞因子谱评估MM患者感染的价值。结果 观察组肿瘤坏死因子-α(TNF-α)、干扰素(IFN)-γ、白细胞介素(IL)-6、IL-10、CRP和PCT水平均高于对照组，差异有统计学意义(P＜0.05)；2组IL-2、IL-4水平比较，差异无统计学意义(P>0.05)。G-菌感染组IL-6、IL-10、CRP和PCT水平高于G+菌感染组和真菌感染组，且G+菌感染组IL-6、CRP水平高于真菌感染组，PCT水平低于真菌感染组，差异有统计学意义(P＜0.05)；感染的3组中IL-2、TNF-α、IFN-γ和IL-4水平比较，差异无统计学意义(P>0.05)。绘制受试者工作特征曲线(ROC)显示，TNF-α、IFN-γ、IL-6、IL-10、CRP和PCT对MM患者感染情况的评估价值均良好，且以IL-6和IL-10的评估价值最为显著；IL-6、IL-10、CRP和PCT评估不同感染类型的MM合并感染患者的价值均良好。结论 相比于传统CRP、PCT等传统指标，CBA技术检测Th1/Th2细胞因子谱对于MM患者早期感染的快速诊断、严重程度评估有重要价值，以TNF-α、IFN-γ、IL-6、IL-10水平均明显升高为特征，且有助于进一步辅助鉴别G+菌和G-菌感染类型。Abstract: Objective To explore the value of cytometric bead array(CBA) in differential diagnosis of infection status and types in patients with multiple myeloma(MM).Methods A retrospective cohort study was used to collect the clinical data of 214 patients with MM admitted to the hospital from January 2019 to December 2022. According to whether had infection these patients was divided into MM patients with infection as the observation group(110 cases), MM patients without infection as the control group(104 cases), of which 110 cases of infection in the observation group, 49 cases of Gram-positive bacteria infection(G+bacteria infection group), 48 cases of Gram-negative bacteria infection(G-bacteria infection group), 13 cases of fungal infection. All samples were tested for Th1/Th2 cytokine profiles using CBA detection technology. The characteristics of Th1/Th2 cytokine profile in uninfected and infected MM patients were observed, and the value of CBA detection of Th1/Th2 cytokine profile in evaluating infection in MM patients was analyzed.Results The levels of tumor necrosis factor-α(TNF-α), interferon(IFN) -γ, interleukin(IL) -6, IL-10, CRP and PCT in the observation group were higher than those in the control group, with a statistical significant difference(P<0.05). There was no statistical significant difference in the levels of IL-2 and IL-4 between the two groups(P>0.05). The levels of IL-6, IL-10, CRP and PCT in G- bacterial infection group were higher than those in G+bacterial infection group and fungal infection group, and the levels of IL-6 and CRP in G+bacterial infection group were higher than those in fungal infection group, and the level of PCT was lower than that in fungal infection group, with a statistical significant difference(P<0.05). There was no statistical significant difference in the levels of IL-2, TNF-α, IFN-γ, and IL-4 among the three groups(P>0.05). The receiver operating characteristic curve(ROC) was drawn and the results showed that TNF-α, IFN-γ, IL-6, IL-10, CRP, and PCT had good evaluation value for infection status in MM patients, with IL-6 and IL-10 being the most significant evaluation values. The value of IL-6, IL-10, CRP and PCT in evaluating MM patients with different infection types was good.Conclusion Compared with traditional indicators such as CRP and PCT, CBA technology for detecting Th1/Th2 cytokine profiles may be of great value for rapid diagnosis and severity assessment of early infection in the patients with MM, characterized by significantly elevated levels of TNF-α, IFN-γ, IL-6, and IL-10, and can further assist in identifying G+and G- bacterial infection types.
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Key words:
- multiple myeloma /
- infection /
- cytometric bead array /
- Th1/Th2 cytokine profile /
- C-reactive protein /
- procalcitonin
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表 1 2组基线资料比较
例 组别 性别
男/女年龄/岁 吸烟史
是/否饮酒史
是/否观察组(n=110) 60/50 56.47±6.81 21/89 15/95 对照组(n=104) 58/46 57.59±7.25 20/84 13/91 χ2/t 0.032 1.159 0.001 0.061 P 0.857 0.248 0.979 0.805 
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表 2 2组Th1/Th2细胞因子谱、CRP和PCT水平比较
pg/mL，X±S 组别 例数 IL-2 TNF-α IFN-γ IL-4 IL-6 IL-10 CRP PCT 观察组 110 1.23±0.67 7.86±1.94 12.84±3.72 1.91±0.50 452.45±104.73 517.39±110.82 4.42±1.27 4.20±0.71 对照组 104 1.08±0.76 5.55±1.79 8.80±2.17 1.85±0.43 198.02±82.89 213.45±91.61 3.55±0.67 3.61±0.70 t 1.534 9.033 9.773 0.924 19.761 21.800 6.309 6.070 P 0.126 ＜0.001 ＜0.001 0.357 ＜0.001 ＜0.001 ＜0.001 ＜0.001
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表 3 不同感染类型的MM合并感染患者Th1/Th2细胞因子谱、CRP和PCT水平
pg/mL，X±S 组别 例数 IL-2 TNF-α IFN-γ IL--4 IL-6 IL-10 CRP PCT G+菌感染组 49 1.25±0.60 8.03±1.89 12.94±3.74 1.95±0.55 431.22±93.42 494.53±86.22 3.45±0.65 4.04±0.74 G-菌感染组 48 1.26±0.73 7.88±1.78 12.71±3.80 1.95±0.47 497.25±93.92 559.32±118.02 3.81±0.60 4.38±0.73 真菌感染组 13 1.05±0.69 7.15±2.62 12.94±3.59 1.63±0.32 367.05±111.39 448.76±113.99 2.93±0.49 4.10±0.29 F 0.556 1.055 0.051 2.316 11.614 7.846 11.652 3.106 P 0.575 0.352 0.950 0.104 ＜0.001 ＜0.001 ＜0.001 0.049
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表 4 各细胞因子评估MM合并感染患者的价值
指标 AUC 95%CI SE P 截断值/(pg/mL) 特异度 灵敏度 约登指数 TNF-α 0.803 0.746~0.861 0.029 ＜0.001 7.050 0.808 0.664 0.472 IFN-γ 0.820 0.763~0.876 0.029 ＜0.001 10.520 0.808 0.718 0.526 IL-6 0.966 0.943~0.989 0.012 ＜0.001 313.100 0.923 0.936 0.859 IL-10 0.978 0.961~0.995 0.009 ＜0.001 329.095 0.913 0.973 0.886 CRP 0.725 0.655~0.796 0.036 ＜0.001 4.410 0.500 0.900 0.400 PCT 0.715 0.647~0.784 0.035 ＜0.001 3.615 0.625 0.782 0.407
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表 5 细胞因子评估不同感染类型的MM合并感染患者的价值
指标 AUC 95%CI SE P 截断值/(pg/mL) 特异度 灵敏度 约登指数 IL-6 0.683 0.578~0.788 0.054 0.002 483.340 0.735 0.583 0.318 IL-10 0.672 0.562~0.782 0.056 0.003 571.645 0.857 0.521 0.378 CRP 0.642 0.533~0.751 0.056 0.016 3.560 0.571 0.625 0.196 PCT 0.635 0.525~0.746 0.056 0.022 4.385 0.714 0.542 0.256
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