Serum Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease

Abstract

Introduction: The goal of this study is to determine whether Advanced glycosylated end-products (AGE), Advanced oxidation protein products (AOPP) and Matrix metalloproteinase 7 (MMP7) could be used as differential biomarkers for idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). Method: Seventy-three patients were enrolled: 29 with IPF, 14 with CTD-ILD, and 30 healthy controls. The study included a single visit by participants. A blood sample was drawn and serum was analysed for AGE using spectrofluorimetry, AOPP by spectrophotometry, and MMP7 using sandwich-type enzyme-linked immunosorbent assay. Results: AGE, AOPP and MMP7 serum levels were significantly higher in both IPF and CTD-ILD patients versus healthy controls; and AGE was also significantly elevated in CTD-ILD compared to the IPF group. AGE plasma levels clearly distinguished CTD-ILD patients from healthy participants (AUC = 0.95; 95% IC 0.86–1), whereas in IPF patients, the distinction was moderate (AUC = 0.78; 95% IC 0.60–0.97). Conclusion: In summary, our results provide support for the potential value of serum AGE, AOPP and MMP7 concentrations as diagnostic biomarkers in IPF and CTD-ILD to differentiate between ILD patients and healthy controls. Furthermore, this study provides evidence, for the first time, for the possible use of AGE as a differential diagnostic biomarker to distinguish between IPF and CTD-ILD. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF and CTD-ILD diagnosis needs to be considered and further explored. Multicentre studies are necessary to understand the role of AGE in differential diagnosis.

Endothelin-1 as a Biomarker of Idiopathic Pulmonary Fibrosis and Interstitial Lung Disease Associated with Autoimmune Diseases

“…Since the accurate diagnosis of ILD implies different therapeutic strategies influencing the management of these patients [ 1 , 2 , 3 , 34 ], the identification of biomarkers for the differential diagnosis between IPF and other ILD is relevant. In this regard, previous studies from our group and others have revealed the potential relevance of biomarkers such as endothelial progenitor cells and advanced glycosylated end-products to discriminate between IPF and ILD associated with connective tissue diseases [ 26 , 35 ]. In a similar manner, the glycoprotein gremlin-1 has been proposed for the differential diagnosis of IPF compared to non-IPF ILD [ 36 ].…”

Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis

“…The presence of UIP is a marker of poor prognosis no matter the specific ILD diagnosis [ 39 ], and elevated MMP7 levels are not specific to IPF [ 40 ]. Aberrant MMP7 expression may be a common feature of end-stage fibrotic disease, and mechanisms relating to its regulation and particularly its activation in the fibrotic epithelium should be further investigated.…”

Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play

“…MMP-7 enhances neutrophil influx to damage AECs, which promotes the development of fibrosis, and then reverses the fibrotic situation by attracting immunosuppressive leukocytes. Many studies have identified MMP-7 as a potential diagnostic and prognostic biomarker for IPF [136][137][138]. Multiple bioinformatic methods have demonstrated that mmp7 gene is significantly correlated with the prognosis and occurrence of IPF.…”