粪便基质金属蛋白酶9及其相关蛋白在婴儿食物过敏中的诊断价值

doi:10.12372/jcp.2024.24e0033

摘要/Abstract

摘要：

目的探索基质金属蛋白酶9(MMP9)及其相关蛋白在婴儿食物过敏（FA）中的诊断价值。方法本研究为巢式病例对照研究，连续纳入2023年4月至2023年10月疑诊FA的婴儿，收集粪便，经口服食物激发试验将入组婴儿分为FA组和非FA组。通过酶联免疫吸附测定法测定粪便MMP9、基质金属蛋白酶组织抑制剂1(TIMP1)和脂质运载蛋白2 (LCN2)的浓度，通过对比粪便总蛋白浓度计算其相对含量，通过受试者工作曲线的曲线下面积（AUC）、灵敏度、特异度等指标评价目标蛋白诊断婴儿FA的准确度。二元logistic回归筛选FA预测因子。结果共纳入FA组69例及非FA组72例。粪便MMP9及TIMP1浓度诊断FA的AUC值分别为0.82和0.78，MMP9及TIMP1相对含量的AUC值分别增加至0.85及0.83。LCN2诊断价值不佳。多因素logistic回归提示粪便MMP9是FA的最佳预测指标。结论粪便MMP9和TIMP1是诊断婴儿FA的有用工具，可以很好的区分FA及类似疾病。

关键词: 食物过敏, 基质金属蛋白酶9, 脂质运载蛋白2, 基质金属蛋白酶组织抑制剂1, 婴儿

Abstract:

Objective To explore the diagnostic value of matrix metalloproteinase 9 (MMP9) and its related proteins for food allergy (FA) in infants. Methods This nested case-control study enrolled infants with suspected FA from April to October 2023. Infant feces were collected and the infants were divided into FA group and non-FA group according to the results of oral food challenges. The fecal MMP9, tissue inhibitor of metalloproteinase 1(TIMP1) and lipocalin 2(LCN2) were measured by enzyme-linked immunosorbent assay, and the relative content was calculated. The area under the ROC curve (AUC), sensitivity and specificity were used to evaluate the accuracy of the target proteins in the diagnosis of infantile FA. We assessed the diagnose value by area under the curve (AUC), sensitivity and specificity. The predictors of FA were screened by binary logistic regression analysis. Results A total of 69 patients in the FA group and 72 patients in the non-FA group were included. The AUC values of fecal MMP9 and TIMP1 concentrations for the diagnosis of FA were 0.82 and 0.78, respectively, and the AUC values of the relative contents of MMP9 and TIMP1 were increased to 0.85 and 0.83, respectively. The diagnostic value of LCN2 is poor. Binary multivariate logistic regression analysis suggested that fecal MMP9 was the best predictor of FA. Conclusion Fecal MMP9 and TIMP1 are useful diagnostic tools for FA in infants, and can distinguish FA from other similar diseases.

Key words: food allergy, matrix metalloproteinase 9, lipocalin 2, tissue inhibitor of metalloproteinase 1, infant

高亚娟, 代妮妮, 张华, 李在玲. 粪便基质金属蛋白酶9及其相关蛋白在婴儿食物过敏中的诊断价值[J]. 临床儿科杂志, 2024, 42(7): 619-625.

GAO Yajuan, DAI Nini, ZHANG Hua, LI Zailing. Diagnostic value of fecal matrix metalloproteinase 9 and its related proteins for food allergy in infants[J]. Journal of Clinical Pediatrics, 2024, 42(7): 619-625.

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参考文献 40

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项目	FA组(n=69)	非FA组(n=72)	统计量	P
年龄M(P₂₅~P₇₅)/月	4.00(2.67~5.53)	4.27(3.93~6.07)	Z=1.32	0.188
性别[n(%)]			χ²=3.08	0.079
男	32(46.38)	44(61.11)
女	37(53.62）	28(38.89）
出生胎龄[M(P₂₅~P₇₅)]/周	39.43(38.71~40.00)	39.43(39.00~40.00)	Z=0.64	0.525
出生身长[M(P₂₅~P₇₅)]/cm	50.00(48.00~51.00)	50.00(48.00~51.00)	Z=1.54	0.117
出生体重[M(P₂₅~P₇₅)]/kg	3.40(3.10~3.60)	3.20(3.00~3.50)	Z=1.11	0.264
剖宫产[n(%)]	32(46.38)	32(44.44)	χ²=0.05	0.818

粪便蛋白	FA组	非FA组	Z值	P
MMP9/ng·mL^-1	8.67(3.95~15.72)	1.49(0.69~3.10)	6.56	<0.001
TIMP/ng·mL^-1	0.82(0.74~1.09)	0.56(0.54~0.74)	5.78	<0.001
LCN2/μg·mL^-1	4.89(2.52~7.80)	3.14(1.65~5.55)	2.90	0.004
粪便总蛋白浓度/mg·mL^-1	1.35(0.98~1.88)	2.32(1.55~3.09)	5.14	<0.001
MMP9相对含量/×10^-6	5.96(2.69~12.49)	0.77(0.19~1.69)	7.09	<0.001
TIMP1相对含量/×10^-6	0.62(0.41~1.08)	0.27(0.16~0.44)	6.57	<0.001
LCN2 相对含量/%	0.35(0.17~0.71)	0.15(0.06~0.25)	4.75	<0.001

粪便蛋白	AUC	灵敏度	特异度	约登指数	最佳阈值
MMP9	0.82	0.80	0.78	0.58	3.58 ng·mL^-1
TIMP1	0.78	0.96	0.49	0.44	0.55 ng·mL^-1
LCN2	0.64	0.59	0.67	0.26	4.17 μg·mL^-1
MMP9相对含量	0.85	0.75	0.83	0.58	2.69×10^-6
TIMP1相对含量	0.82	0.68	0.83	0.51	0.51
LCN2相对含量	0.73	0.59	0.79	0.39	0.28%

变量	β	SE	χ²值	P	OR	95%CI
MMP9	0.18	0.05	3.65	<0.001	1.19	1.09~1.32
TIMP1	1.30	0.78	1.67	0.094	3.67	0.89~19.27
LCN2	0.002	0.02	0.10	0.921	1.01	0.97~1.04