鉴定MMP28作为特发性肺纤维化鉴别诊断的生物标志物,PLOS ONE

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鉴定MMP28作为特发性肺纤维化鉴别诊断的生物标志物
PLOS ONE ( IF 2.9 ) Pub Date : 2018-09-12 , DOI: 10.1371/journal.pone.0203779
Mariel Maldonado , Ivette Buendía-Roldán , Vanesa Vicens-Zygmunt , Lurdes Planas , Maria Molina-Molina , Moisés Selman , Annie Pardo

背景和目标

特发性肺纤维化（IPF）是一种病因不明的进行性疾病。该诊断是基于通过高分辨率计算机断层扫描和/或组织学确定常见的间质性肺炎的模式。但是，在其他纤维化性肺部疾病中也可以观察到类似的模式，准确的诊断仍然具有挑战性。对有助于鉴别诊断的生物标志物的研究很少，并且仍处于探索阶段。我们的目的是评估基质金属蛋白酶（MMP）-28，它与伤口异常愈合有关，作为区分IPF和纤维化非IPF患者的生物标志物。

方法

通过免疫组织化学检查MMP28在肺中的细胞定位，并通过ELISA测量其在两个不同人群中的血清浓度。该派生队列包括82例IPF和69例纤维化非IPF患者。验证队列涉及42例IPF和41例纤维化非IPF患者。

结果

MMP28主要在IPF肺中检测到，并位于上皮细胞中。在两个队列中，IPF的血清MMP28浓度均显着高于非IPF（主要是与自身免疫性疾病和慢性超敏性肺炎相关的肺纤维化）和健康对照组（ANOVA，p <0.0001）。派生队列的AUC为0.718（95％CI，0.635–0.800）。截断点为4.5 ng / mL，OR为5.32（95％CI，2.55-11.46），敏感性和特异性分别为70.9％和69％。验证队列的AUC为0.690（95％CI，0.581–0.798），或4.57（95％CI，1.76–12.04），敏感性和特异性分别为69.6％和66.7％。有趣的是，我们发现在HRCT上具有明确UIP模式的IPF患者的MMP28血清浓度高于具有相同模式的非IPF患者（7.8±4.4对4.9±4.4； p = 0.04）。

结论

这些发现表明，MMP28可能是提高IPF诊断确定性的有用生物标志物。

"点击查看英文标题和摘要"

Identification of MMP28 as a biomarker for the differential diagnosis of idiopathic pulmonary fibrosis

Background and objective

Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease of unknown etiology. The diagnosis is based on the identification of a pattern of usual interstitial pneumonia either by high resolution computed tomography and/or histology. However, a similar pattern can be observed in other fibrotic lung disorders, and precise diagnosis remains challenging. Studies on biomarkers contributing to the differential diagnosis are scanty, and still in an exploratory phase. Our aim was to evaluate matrix metalloproteinase (MMP)-28, which has been implicated in abnormal wound healing, as a biomarker for distinguishing IPF from fibrotic non-IPF patients.

Methods

The cell localization of MMP28 in lungs was examined by immunohistochemistry and its serum concentration was measured by ELISA in two different populations. The derivation cohort included 82 IPF and 69 fibrotic non-IPF patients. The validation cohort involved 42 IPF and 41 fibrotic non-IPF patients.

Results

MMP28 was detected mainly in IPF lungs and localized in epithelial cells. In both cohorts, serum concentrations of MMP28 were significantly higher in IPF versus non-IPF (mostly with lung fibrosis associated to autoimmune diseases and chronic hypersensitivity pneumonitis) and healthy controls (ANOVA, p<0.0001). The AUC of the derivation cohort was 0.718 (95%CI, 0.635–0.800). With a cutoff point of 4.5 ng/mL, OR was 5.32 (95%CI, 2.55–11.46), and sensitivity and specificity of 70.9% and 69% respectively. The AUC of the validation cohort was 0.690 (95%CI, 0.581–0.798), OR 4.57 (95%CI, 1.76–12.04), and sensitivity and specificity of 69.6% and 66.7%. Interestingly, we found that IPF patients with definite UIP pattern on HRCT showed higher serum concentrations of MMP28 than non-IPF patients with the same pattern (7.8±4.4 versus 4.9±4.4; p = 0.04). By contrast, no differences were observed when IPF with possible UIP-pattern were compared (4.7±3.2 versus 3.9±3.0; p = 0.43).