Serum amyloid A: a new biomarker in Idiopathic Pulmonary Fibrosis

Background: Lipid metabolism has been demonstrated altered in different interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis (IPF). Serum amyloid A (SAA) is an acute phase protein mainly produced by the liver in response to proinflammatory cytokines. Few data are available on SAA levels in patients with IPF, a chronic progressive lung disease associated with a poor survival and a radiological and histological pattern of usual interstitial pneumonia (UIP). The clinical course of IPF is unpredictable. To date, we don't have a marker of severity and prognosis capable of establishing the evolution of IPF early. Objectives: We compared SAA serum levels in IPF patients to other ILD groups, to definite the potential value of this protein as a biomarker of fibrosis and its specificity in IPF. Our aim is to demonstrate the role of the lipid metabolism in the fibrotic process, especially the role of the apolipoprotein SAA as a biomarker of IPF that can predict clinical course, prognosis and survival of IPF patients. Materials and methods: We enrolled 185 patients (40 stable IPF, 8 IPF with acute exacerbation, 30 sarcoidosis, 30 chronic HP, 17 cystic ILDs (PLCH&LAM), 6 NSIP, 9 UIP non-IPF, 16 SSc-ILD, 6 COPD with pulmonary emphysema, 6 other ILDs, 17 healthy controls), monitored at Siena Regional Centre for ILDs and at the Respiratory Department of the Saint Anna Hospital at University of Ferrara. IPF patients were prevalently male, ex-smokers and over 65 years of age. Clinical, functional, radiological and immunological data were collected from all patients. Results: IPF patients have significantly higher SAA serum levels than the other ILDs (61,64 ± 8,52 mcg/ml). In the groups IPF, AE-IPF, UIP-non IPF, emphysema and other-ILDs patients were predominantly males and older than the other groups of patients (over 65 years of age). The ANOVA test showed a clear and statistical significant difference between SAA serum levels in the IPF group vs healthy controls (p<0.0002), which indicates that SAA is a disease marker. A ROC curve analysis showed that IPF patients have statistical significance higher SAA serum levels than SSc-ILD with a progressive fibrosis, identifying a cut-off value (45,21 mcg/ml, p<0,0001, AUC 97,6 with specificity 100%). This data indicates that a patient with a progressive fibrosis with serum SAA levels above that cut-off is more likely an IPF than another progressive fibrosis with a pattern UIP or another radiological pattern. The difference in serum SAA concentration in the IPF and AE-IPF groups was statistically significant (p<0.002). By performing a ROC curve of SAA in AE-IPF vs stable IPF we detected a cut-off 48,84 mcg/ml highly specific for acute exacerbation (AUC: 90.4%; p<0,0024; Se: 87,5%; Sp: 92,31%). These results show how serum SAA levels are higher in IPF patients in the stable phase compared to those with acute exacerbation, suggesting a role for SAA as a biomarker of fibrosis. Conclusions: SAA could be considered a potential specific biomarker for IPF that can predict clinical course and prognosis of patients. SAA could discriminate an inflammatory ILD from a pulmonary progressive fibrosis mainly for IPF (which is a progressive fibrosis by definition). Monitoring serum levels could be useful to identify patients with rapidly progressive IPF disease phenotype or at risk of acute exacerbation. SAA may play a crucial role in the regulation of lipid metabolism and production of MMPs in IPF. May be SAA could become a potential target for IPF treatment, including via apolipoproteins.