粪钙卫蛋白、C反应蛋白、白介素-6在诊断克罗恩病患者消化道黏膜损伤状态中的价值

doi:10.3969/j.issn.1674-8115.2022.03.010

摘要/Abstract

摘要：

目的·探讨粪钙卫蛋白（fecal calprotectin，FC）、C反应蛋白（C-reactive protein，CRP）、白介素-6（interleukin-6，IL-6）在诊断克罗恩病患者消化道黏膜损伤状态中的应用价值。方法·选取2019年6月—2020年6月上海交通大学医学院附属仁济医院收治的克罗恩病患者52例。根据消化道内镜评估结果将患者分为黏膜未损伤组和黏膜损伤组，比较2组之间的临床特征。通过流式微球分析技术法检测IL-6水平，通过免疫荧光层析技术检测粪便中FC含量，通过散射比浊法检测患者全血中CRP含量。患者在入院24 h内检测外周血IL-6、CRP，72 h内检测FC；比较2组之间的差异。通过多因素Logistic回归分析黏膜损伤的独立影响因素。通过受试者操作特征曲线（receiver operating characteristic curve，ROC曲线）判断IL-6、CRP、FC及联合指标对于判断黏膜损伤的诊断价值。结果·52例患者中黏膜未损伤组21例，黏膜损伤组31例，2组患者的年龄、性别间差异均无统计学意义，蒙特利尔分型中仅疾病行为分布差异有统计学意义（P<0.05）。黏膜损伤组患者的IL-6、CRP、FC水平分别为11.1（3.67，17.54）pg/mL、8.02（2.13，30.96）mg/L、448.4（212.90，639.50）μg/g，均显著高于黏膜未损伤组（均P<0.05）。Logistic回归分析结果提示，仅有FC是克罗恩病患者消化道黏膜受损的独立影响因素（OR=1.006， P<0.05）。IL-6、CRP和FC单项指标判断消化道黏膜损伤的ROC曲线下面积（area under the curve，AUC）分别为0.71、0.88和0.85（均P<0.05）；FC+CRP和FC+IL-6双项联合检测时AUC分别为0.91和0.84（均P<0.05）；FC+IL-6+CRP三项联合检测时AUC为0.92（P<0.05）。通过比较双项联合检测与三项联合检测的ROC曲线发现，FC+CRP与FC+IL-6+CRP的AUC差异无统计学意义，而FC+IL-6与FC+IL-6+CRP之间差异有统计学意义（P=0.045）。同时，FC+CRP与FC+IL-6+CRP的敏感度和特异度均分别为77%和100%。结论·FC和CRP联合检测，以及FC、IL-6和CRP联合检测均能有效判断克罗恩病患者消化道黏膜损伤情况，诊断价值相当；基于简便性及检测成本，临床上更推荐使用FC和CRP联合检测。

关键词: 克罗恩病, 粪钙卫蛋白, C反应蛋白, 白介素-6, 黏膜损伤

Abstract:

Objective·To investigate the values of fecal calprotectin (FC), C-reactive protein (CRP) and interleukin 6 (IL-6) in diagnosing the gastrointestinal mucosal injury in the patients with Crohn′s disease (CD).

Methods·A total of 52 CD patients admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2019 to June 2020 were enrolled in the study. The patients were divided into uninjured mucosa group and injured mucosa group based on the gastrointestinal endoscopic results, and the clinical features of the two groups were compared. The level of IL-6 was detected by cytometric bead array. The content of FC was detected by immunofluorescence chromatography. CRP in the whole blood was detected by nephelometry. IL-6 and CRP were detected within 24 h of admission, while FC was detected within 72 h. The results were compared between the two groups. The independent influence factors of mucosal injury were analyzed by multivariate Logistic regression. The receiver operating characteristic (ROC) curve was used to determine the values of IL-6, CRP, FC and their combination in judging mucosal injury.

Results·Among the 52 patients, there were 21 patients in the uninjured mucosa group and 31 in the injured mucosa group. There were no significant differences in the age and gender between the two groups. The significant difference was only identified in the distribution of disease behavior in the Montreal Classification (P<0.05). The levels of IL-6, CRP and FC in the injured mucosa group were 11.1 (3.67, 17.54) pg/mL, 8.02 (2.13, 30.96) mg/L and 448.4 (212.90, 639.50) μg/g, respectively, which were significantly higher than those in the uninjured mucosa group (P<0.05). Logistic regression analysis suggested that only FC was an independent factor for judging the injured status of gastrointestinal mucosa in the CD patients (OR=1.006, P<0.05). The areas under the ROC curves (AUCs) of IL-6, CRP and FC for judging the state of gastrointestinal mucosal injury were 0.71, 0.88 and 0.85, respectively (all P<0.05). The AUCs of FC+CRP and FC+IL-6 were 0.91 and 0.84, respectively (both P<0.05). The AUC of FC+IL-6+CRP was 0.92 (P<0.05). By comparing the ROC curves of the two-item combined detection and the three-item combined detection, no significant difference could be identified in the AUC between FC+CRP and FC+IL-6+CRP. However, a significant difference was identified between FC+IL-6 and FC+IL-6+CRP (P=0.045). Meanwhile, the sensitivities and specificities of both FC+CRP and FC+IL-6+CRP were 77% and 100%, respectively.

Conclusion·The combined detection of FC and CRP, as well as the combined detection of FC, IL-6 and CRP, can effectively judge the gastrointestinal mucosal injury in patients with CD, the diagnostic values of which are similar; based on the simplicity and the cost, the combined detection of FC and CRP is more recommended clinically.

Key words: Crohn′s disease (CD), fecal calprotectin (FC), C-reactive protein (CRP), interleukin-6 (IL-6), mucosal injury

中图分类号:

R574.1

马继荣, 沈薇, 顾怡, 沈文艳, 周景艺. 粪钙卫蛋白、C反应蛋白、白介素-6在诊断克罗恩病患者消化道黏膜损伤状态中的价值[J]. 上海交通大学学报（医学版）, 2022, 42(3): 331-336.

MA Jirong, SHEN Wei, GU Yi, SHEN Wenyan, ZHOU Jingyi. Values of fecal calprotectin, C-reactive protein and interleukin-6 in diagnosing gastrointestinal mucosal injury in patients with Crohn's disease[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(3): 331-336.

图/表 6

参考文献 13

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Clinical feature	Uninjured mucosal group （n=21）	Injured mucosal group （n=31）	P value
Age/year	30.2±9.5	34.0±10.0	0.173
Male/n （%）	12 （57.1）	16 （51.6）	0.695
Age of diagnosis/n （%）			0.700
A₁	0 （0）	0 （0）
A₂	16 （76.2）	25 （80.7）
A₃	5 （23.8）	6 （19.3）
Lesion site/n （%）			0.215
L₁	8 （38.1）	6 （19.4）
L₂	3 （14.3）	4 （12.9）
L₃	9 （42.8）	21 （67.7）
L₄	0 （0）	0 （0）
L₃+L₄	1 （4.8）	0 （0）
Disease behavior/n （%）			0.019
B₁	11 （52.4）	16 （51.6）
B₂	4 （19.0）	14 （45.2）
B₃	5 （23.8）	0 （0）
B₂+B₃	1 （4.8）	1 （3.2）
Combined with perianal lesion （p）/n （%）	15 （71.4）	17 （54.8）	0.228

Clinical feature	Uninjured mucosal group （n=21）	Injured mucosal group （n=31）	P value
Age/year	30.2±9.5	34.0±10.0	0.173
Male/n （%）	12 （57.1）	16 （51.6）	0.695
Age of diagnosis/n （%）			0.700
A₁	0 （0）	0 （0）
A₂	16 （76.2）	25 （80.7）
A₃	5 （23.8）	6 （19.3）
Lesion site/n （%）			0.215
L₁	8 （38.1）	6 （19.4）
L₂	3 （14.3）	4 （12.9）
L₃	9 （42.8）	21 （67.7）
L₄	0 （0）	0 （0）
L₃+L₄	1 （4.8）	0 （0）
Disease behavior/n （%）			0.019
B₁	11 （52.4）	16 （51.6）
B₂	4 （19.0）	14 （45.2）
B₃	5 （23.8）	0 （0）
B₂+B₃	1 （4.8）	1 （3.2）
Combined with perianal lesion （p）/n （%）	15 （71.4）	17 （54.8）	0.228

Item	IL-6	CRP	FC
IL-6	‒	0.715^①	0.389^②
CRP	0.715^①	‒	0.608^①
FC	0.389^②	0.608^①	‒

Item	IL-6	CRP	FC
IL-6	‒	0.715^①	0.389^②
CRP	0.715^①	‒	0.608^①
FC	0.389^②	0.608^①	‒

Item	B	SE	Wald	P value	OR	95%CI
IL-6	-0.023	0.021	1.139	0.286	0.977	0.937‒1.019
CRP	0.322	0.211	2.490	0.115	1.395	0.923‒2.109
FC	0.006	0.002	6.288	0.012	1.006	1.001‒1.011
Disease behavior	0.171	0.592	0.083	0.773	1.186	0.372‒3.789
Constant	-2.324	1.361	2.915	0.088	0.098