Correlation analysis between different vitamin D levels and immune inflammatory indicators in elderly patients with sepsis
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摘要:
目的 探讨老年脓毒症患者血清维生素D（ViTamin D，VD）水平差异与免疫炎症指标的相关性，为老年脓毒症患者免疫功能治疗寻找新靶点。 方法 收集2020年1月至2022年12月昆医大附一院ICU老年脓毒症患者103例（65～99岁），按照VD3缺乏诊断标准分为两个组：VD3缺乏组（42例），VD3严重缺乏组（61例）。通过比较入院时血清25-（OH）-D3（VD3），免疫功能相关指标（血常规、感染相关蛋白、12项细胞因子联合检测、淋巴细胞及亚群绝对计数分析、感染相关免疫细胞、免疫球蛋白及补体定量测定）、病情严重程度及预后指标（APACHE-II评分、SOFA评分、住ICU时间、28d死亡率）的差异，进行相关性分析。结果（1）老年脓毒症患者血清VD3水平低，VD缺乏组（45例），VD严重缺乏组（63例），无VD正常和不足组患者，VD严重缺乏患者APACHE-II评分、SOFA评分及28 d死亡率高于VD缺乏患者，且与血清VD3水平均呈负相关（P < 0.001），而ICU住院时间两组间差异无统计学意义；（2）VD缺乏组WBC、PCT、CRP、CD4/CD8均低于VD严重缺乏组（P均 < 0.05），而IL-6、IL-10，CD45+ 、CD3+/CD45+、CD19+Abs均高于VD严重缺乏组（P均 < 0.05）；VD缺乏组中VD3水平与CD45+呈正相关（P均 < 0.05），而与IL-6、IL-10、PCT、CRP均呈负相关（P均 < 0.05）；在VD严重缺乏组中存在相关性指标较少且相关性强度不如VD缺乏组。 结论 （1）老年脓毒症患者VD水平普遍较低，水平越低病情越严重，预后越差；（2）老年脓毒症中，与VD严重缺乏患者相比，VD缺乏患者的炎症水平低，而细胞免疫反应更强，相关性更强，提示老年脓毒症患者不同的VD3水平对免疫炎症反应的影响可能是不同的。 -
关键词:
- 25-羟基维生素D3 /
- 免疫功能 /
- 脓毒症 /
- 老年患者 /
- 预后
Abstract:Objective To explore the correlation between serum vitamin D （VD3） level differences and immune inflammatory markers in elderly sepsis patients, aiming to identify new therapeutic targets for immune function in these patients. Method A total of 103 elderly patients with sepsis（aged 65-99 years） in the ICU of the First Affiliated Hospital of Kunming Medical University from January 2020 to December 2022 were collected and divided into two groups according to the diagnostic criteria for VD3 deficiency: VD3 deficiency group （42 cases） and VD3 severe deficiency group （61 cases）. Correlation analysis was conducted by comparing the differences in serum 25- （OH） - D3 （VD3） levels , immune function-related indicators upon admission （blood routine, infection-related proteins, combined detection of 12 cytokines, absolute count analysis of lymphocytes and subgroups, quantitative determination of infection-related immune cells, immunoglobulin, and complement）, illness severity, and prognostic indicators （APACHE-II score, SOFA score, duration of ICU stay, and 28-day mortality rate）. Result （1） Serum VD3 levels were lower in elderly patients with sepsis, with 42 cases in the VD3 deficiency group, 61 cases in the the VD3 severe deficiency group. No patient was in the VD3 normal or insufficient group. Patients with severe VD3 deficiency had higher APACHE-II scores, SOFA scores, and 28- day mortality rates than those with VD3 deficiency, and these scores were negatively correlated with serum VD3 levels （P < 0.001）, while the difference in ICU stay duration between the two groups was not statistically significant; （2） WBC, PCT, CRP, and CD4/CD8 in the VD3 deficiency group were all lower than those in the VD3 severe deficiency group （P values < 0.05）, while IL-6, IL-10, CD45+, CD3+/CD45+, and CD19+Abs were all higher than those in the VD3 severe deficiency group （P values < 0.05）; In the VD3 deficiency group, VD3 levels were positively correlated with CD45+（P values < 0.05 for all）, while negatively correlated with IL-6, IL-10, PCT, and CRP （P values < 0.05 for all）; In the VD3 severe deficiency group, there were fewer correlation indicators and the correlation strength was not as strong as that in the VD deficiency group. Conclusion （1） Elderly patients with sepsis generally have lower levels of VD3, with lower levels associated with more severe illness and poorer prognosis; （2） In elderly sepsis patients, compared to patients with severe VD3 deficiency, patients with VD3 deficiency have lower levels of inflammation, stronger cellular immune response, and stronger correlation, suggesting that the effects of different VD3 levels on immune inflammatory responses may vary in elderly sepsis patients. -
Key words:
- 25-hydroxyvitamin D3 /
- Immune function /
- Sepsis /
- Elderly patients /
- Prognosis
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表 1 VD3严重缺乏组和VD3缺乏组患者一般资料比较[（$\bar x \pm s $/n （%）]
Table 1. Comparison of general information between VD3 severe deficiency group and VD3 deficiency group [（$ \bar x \pm s$/n （%）]
项目 缺乏组 严重缺乏组 t/ χ2 P （男/女） 23/9（71.9/28.1） 54/17（76.1/23.9） 0.169 0.827 APACHE-II评（分） 19.19 ± 1.46 28.35 ± 0.92 4.336 0.002* SOFA评分（分） 13.41 ± 1.97 22.39 ± 1.36 3.147 0.014* ICU 住院时间（d） 13.07 ± 3.70 15.12 ± 2.15 0.826 0.410 （存活/死亡） 22/10（68.8/31.2） 33/38（46.5/53.5） 4.524 < 0.001* *P < 0.05。 
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表 2 老年脓毒症患者VD3与APACHE-II评分、SOFA评分、住院时间相关性分析
Table 2. Correlation analysis of VD3 with APACHE-II score, SOFA score，and duration of hospitalization in elderly sepsis patients
指标 老年组（n=103） r P APACHE-II评分 −0.780 < 0.001* SOFA评分 −0.551 < 0.001* ICU住院时间 −0.216 0.437 *P < 0.05。
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表 3 老年患者VD与免疫炎症指标相关性分析
Table 3. Correlation analysis between VD3 and immune inflammatory indicators in elderly sepsis patients
实验室资料 r P WBC （×109/L） 0.288 0.101 NEUT（×109/L） 0.055 0.443 LYMPH（×109/L） 0.369 0.017* PCT（ng/mL） −0.463 0.021* HS-CRP（mg/L） −0.398 0.037* IL-1β（pg/mL） −0.265 0.109 IL-2（pg/mL） −0.195 0.244 IL-4（pg/mL） −0.206 0.241 IL-5（pg/mL） −0.117 0.302 IL-6（pg/mL） −0.437 0.011* IL-8（pg/mL） −0.301 0.041* IL-10（pg/mL） −0.641 0.002* IL-12P10（pg/mL） −0.118 0.145 IL-17（pg/mL） −0.235 0.294 IFN-α（pg/mL） −0.194 0.056 IFN-γ（pg/mL） 0.002 0.982 TNF-α（pg/mL） −0.219 0.413 CD45+ 个/µL 0.803 0.041* CD3+/CD45+个/µL 0.514 0.013* CD3+CD4+/CD45个/µL 0.195 0.064 （CD19+Abs）个/µL 0.125 0.079 CD4/CD8 −0.017 0.814 CD64 −0.390 0.029* mHLA-DR% −0.228 0.051 IgG（g/L） 0.085 0.303 IgA（g/L） −0.061 0.396 IgM（g/L） −0.121 0.191 *P < 0.05。
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表 4 老年脓毒症患者VD3与免疫炎症指标比较 [$\bar x \pm s $/M（P25，P75）]
Table 4. Comparison of VD3 with immune inflammatory markers in elderly sepsis patients [$\bar x \pm s $/M（P25，P75）]
实验室资料 缺乏组 严重缺乏组 t/z P WBC （×109/L） 12.04 ± 4.03 20.12 ± 6.03 −2.757 < 0.001* NEUT（×109/L） 10.97 ± 1.76 14.19 ± 2.99 0.416 0.211 LYMPH（×109/L） 0.91 ± 0.36 0.72 ± 0.29 0.114 0.102 PCT（ng/mL） 69.12 ± 21.05 112.05 ± 18.56 −0.647 0.021* HS-CRP（mg/L） 65.24 ± 14.23 198.12 ± 66.35 −1.410 0.002* IL-1β（pg/mL） 5.36 ± 1.23 4.78 ± 1.69 −1.253 0.562 IL-2（pg/mL） 2.24 ± 1.05 3.25 ± 2.04 −0.952 0.254 IL-4（pg/mL） 0.98 ± 0.44 1.14 ± 0.95 −0.452 0.698 IL-5（pg/mL） 1.05（0.63−10.17） 2.11（0.52−12.03） −0.145 0.317 IL-6（pg/mL） 982.12 ± 123.04 652.98 ± 45.15 1.159 0.027* IL-8（pg/mL） 41.25 ± 12.41 39.28 ± 11.85 −0.518 0.605 IL-10（pg/mL） 47.11 ± 13.14 34.56 ± 9.15 0.724 0.019* IL-12P10（pg/mL） 1.75 ± 0.98 1.99 ± 1.25 −0.581 0.336 IL-17（pg/mL） 8.69 ± 2.37 6.98 ± 1.69 0.124 0.258 IFN-α（pg/mL） 2.01 ± 1.36 1.85 ± 0.93 −0.119 0.906 IFN-γ（pg/mL） 2.94（1.69−5.37） 3.18（2.27−4.85） −1.789 0.074 TNF-α（pg/mL） 3.76 ± 1.32 3.97 ± 1.50 −0.811 0.994 CD45+ 个/uL 996.05 ± 220.26 603.36 ± 110.45 0.875 0.033* CD3+/CD45+个/µL 699.01 ± 90.25 498.35 ± 132.01 0.727 0.033* CD3+CD4+/CD45个/ul 71.23 ± 26.35 69.32 ± 13.06 0.532 0.106 CD19+Abs个/µL 156.69 ± 32.01 94.36 ± 24.16 0.862 0.019* CD4/CD8 1.96 ± 0.45 0.77 ± 0.45 0.741 0.032* CD64 34.25 ± 15.26 29.25 ± 10.14 −0.262 0.793 mHLA-DR% 47.62 ± 12.06 54.92 ± 15.15 −0.527 0.605 IgG（g/L） 14.5（5.83−18.72） 8.71（6.38−15.29） −1.757 0.439 IgA（g/L） 3.25（1.26−5.15） 2.55（1.50−4.90） −0.774 0.271 IgM（g/L） 0.60（0.51−0.97） 0.66（0.52−0.85） −1.185 0.159 *P < 0.05。
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表 5 老年患者VD不同水平组间免疫炎症指标相关性分析（1）
Table 5. Correlation analysis of immune inflammatory indicators between different levels of VD3 in elderly sepsis patients（1）
实验室资料 缺乏组 实验室资料 严重缺乏组 r P r P WBC （×109/L） −0.822 0.011* WBC （×109/L） 0.170 0.164 NEUT（×109/L） −0.036 0.766 NEUT（×109/L） 0.146 0.230 LYMPH#（×109/L） 0.331 0.120 LYMPH（×109/L） 0.184 0.131 PCT（ng/mL） −0.516 0.049* PCT（ng/mL） −0.276 0.137 HS-CRP（mg/L） −0.573 0.014* HS-CRP（mg/L） −0.397 0.037* IL-1β（pg/mL） −0.254 0.259 IL-1β（pg/mL） −0.165 0.359 IL-2（pg/mL） −0.158 0.301 IL-2（pg/mL） −0.224 0.125 IL-4（pg/mL） −0.369 0.189 IL-4（pg/mL） −0.301 0.241 IL-5（pg/mL） −0.228 0.164 IL-5（pg/mL） −0.356 0.131 IL-6（pg/mL） −0.486 0.011* IL-6（pg/mL） −0.109 0.091 IL-8（pg/mL） −0.358 0.023* IL-8（pg/mL） −0.141 0.094
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表 5 老年患者VD不同水平组间免疫炎症指标相关性分析（2）
Table 5. Correlation analysis of immune inflammatory indicators between different levels of VD3 in elderly sepsis patients（2）
实验室资料 缺乏组 实验室资料 严重缺乏组 r P r P IL-10（pg/mL） −0.697 0.013* IL-10（pg/mL） −0.086 0.986 IL-12P10（pg/mL） −0.214 0.159 IL-12P10（pg/mL） −0.226 0.225 IL-17（pg/mL） −0.257 0.214 IL-17（pg/mL） −0.159 0.156 IFN-α（pg/mL） −0.055 0.651 IFN-α（pg/mL） 0.026 0.883 IFN-γ（pg/mL） −0.174 0.154 IFN-γ（pg/mL） −0.224 0.064 TNF-α（pg/mL） −0.156 0.243 TNF-α（pg/mL） −0.117 0.249 CD45+ 个/ul 0.753 0.043* CD45+ 个/ul 0.178 0.527 CD3+/CD45+个/ul 0.641 0.048* CD3+/CD45+个/ul 0.167 0.586 CD3+CD4+/CD4个/ul −0.292 0.098 CD3+CD4+/CD45个/ul 0.144 0.346 （CD19+Abs）个/ul 0.563 0.039* （CD19+Abs）个/ul 0.109 0.372 CD4/CD8 0.041 0.742 CD4/CD8 0.210 0.047* CD64 −0.491 0.021* CD64 −0.293 0.032* mHLA-DR% −0.099 0.465 mHLA-DR% −0.053 0.702 IgG（g/L） 0.126 0.352 IgG（g/L） −0.116 0.334 IgA（g/L） 0.002 0.985 IgA（g/L） −0.008 0.948 IgM（g/L） −0.159 0.191 IgM（g/L） −0.045 0.715 *P < 0.05。
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