PURPOSE: The idiopathic interstitial pneumonias (IIPs) including idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and cryptogenic organizing pneumonia (COP) are an important subset of the broader category of interstitial lung diseases. Among these, IPF and NSIP have provoked the most debate and discussion, because patients with NSIP that clinically mimics IPF have a better prognosis than patients with IPF and respond to immunosuppressive treatment. Thus it is important to differentiate between IPF and NSIP. Myeloid-related protein (MRP)-14 has been reported to be associated with pulmonary inflammatory disorders, however the role of MRP-14 in the pathogenesis of IIPs remains unclear. The present study was aimed to investigate the role of MRP-14 in the pathogenesis of IIPs and examine whether MRP-14 could be a disease biomarker to assess the types of IIPs.
METHODS: We enrolled 63 patients with IIPs (28 with IPF, 15 with NSIP, 20 with COP) and 23 healthy individuals. MRP-14 levels in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assays. The association between MRP-14 levels and clinical parameters were analyzed. Localization of MRP-14 in the lung was also evaluated by immunohistochemistry.
RESULTS: Serum and BALF levels of MRP-14 were significantly elevated in patients with IPF compared with NSIP, COP and healthy individuals. The levels of MRP-14 in serum and BALF from patients with IPF were significantly associated with the number of neutrophils in BALF. MRP-14 immunoreactivity was localized mainly in macrophages and neutrophils in lung specimens from patients with IPF. The ROC curve analysis showed that both serum and BALF MRP-14 levels had a favorable specificity and sensitivity to distinguish IPF from NSIP compared with other markers of interstitial pneumonia.
CONCLUSIONS: In conclusion, S100A9 may be a possible candidate for a biomarker to discriminate between IPF and NSIP. Further studies are required to elucidate the role of S100A9 in IPF. MRP-14 might play a role in the pathogenesis of IPF via contributing neutrophilic lung inflammation.
CLINICAL IMPLICATIONS: S100A9 may be a possible candidate for a biomarker of IPF.
DISCLOSURE: The following authors have nothing to disclose: Noriho Sakamoto, Yuji Ishimatsu, Tomoyuki Kakugawa, Shota Nakashima, Atsuko Hara, Shintaro Hara, Hanako Fujita, Hiroshi Mukae, Shigeru Kohno
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