D23-19 Exploring Serum Desmosine and Pyridinoline as Novel Biomarkers for Idiopathic Pleuroparenchymal Fibroelastosis

Rationale Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare type of interstitial lung disease (ILD) characterized by upper lobe-predominant subpleural fibrosis and physical features such as a flat chest and marked emaciation, suggesting underlying connective tissue abnormalities. Histopathological examination reveals prominent deposition of collagen and excessive accumulation of elastin. iPPFE may present as a non-progressive apical cap or as a progressive form often complicated by pneumothorax and poor prognosis. Diagnostic and prognostic biomarkers are therefore needed to differentiate these clinical courses. We have been conducting a multicenter prospective cohort study of iPPFE in Japan, in which serum samples are collected. Pyridinoline and desmosine, cross-linking compounds derived from collagen and elastin metabolism, can be measured in serum. We investigated their potential utility as serum biomarkers for iPPFE. Methods Our iPPFE registry included 215 cases from 36 institutions in Japan. Serum levels of pyridinoline and deoxypyridinoline, cross-linking compounds of collagen, and desmosine/isodesmosine, cross-linking compounds of elastin, were measured by LC-MS in all 215 iPPFE cases. As control groups, we analyzed serum samples from 61 patients with other ILDs and 198 healthy subjects using the same assays. Results Serum levels of desmosine/isodesmosine, pyridinoline, and deoxypyridinoline were all significantly higher in patients with iPPFE than in healthy controls (p < 0.01). When compared with other ILD groups, only deoxypyridinoline was significantly elevated in the iPPFE group (p < 0.01). Logistic regression analysis including age and sex revealed that age (odds ratio 0.907; 95% CI 0.868-0.947; p < 0.01) and desmosine/isodesmosine (odds ratio 48.20; 95% CI 3.540-656.0; p < 0.01) were significantly associated with iPPFE. Using the regression coefficients to adjust desmosine/isodesmosine levels for age, receiver operating characteristic (ROC) curve analysis yielded an AUC of 0.756 (95% CI 0.677-0.835) with a sensitivity of 72.7% and specificity of 69.1%, suggesting that age-adjusted serum desmosine/isodesmosine may serve as a useful diagnostic biomarker for iPPFE. In a Cox regression analysis to identify prognostic factors in iPPFE, the serum pyridinoline level was significantly associated with mortality or lung transplantation (hazard ratio 2.44, 95% CI 1.73-3.45, p < 0.01) and remained an independent predictor after adjustment for BMI, albumin, KL-6, SP-D, and %FVC. Conclusion Serum desmosine and pyridinoline may serve as diagnostic and prognostic biomarkers, respectively, for iPPFE.