Propeptide levels of type III and type I procollagen in the serum and bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis

Abstract

No single test is available to reliably assess the activity or prognosis of pulmonary sarcoidosis. In this study, we have evaluated two procollagen markers, aminoterminal propeptide of type III procollagen (PIIINP) and carboxyterminal propeptide of type I procollagen (PICP) in serum and bronchoalveolar lavage fluid (BALF) and compared them to other disease markers of pulmonary sarcoidosis, such as serum level of angiotensin converting enzyme (S-ACE) or serum interleukin-2 receptor (S-IL-2R). Bronchoalveolar lavage was performed in 40 sarcoidosis patients without (stages 0-I) and 20 patients with lung parenchymal involvement (stages II-III), as well as in 17 controls. Serum (S)- and BALF-PIIINP and PICP, S-ACE, S-IL-2R, BALF-albumin, BALF-lymphocytes and mast cells were determined in these patients. BALF-PIIINP was clearly and S-PIIINP slightly elevated in sarcoidosis compared to the controls. Similarly BALF-PICP, but not S-PICP, was significantly higher in sarcoidosis. BALF-PIIINP, but not BALF-PICP correlated with S-ACE and S-IL-2R levels. Patients with lung parenchymal disease had higher S-ACE and BALF-PIIINP, but neither S-IL-2R, S-PIIINP nor S- or BALF-PICP were elevated. S-PIIINP and S-IL-2R but not S-ACE were higher in symptomatic than nonsymptomatic patients. Symptomatic patients with parenchymal disease had elevated BALF-PIIINP whereas in the symptomatic nonparenchymal group S-PIIINP was elevated. In conclusion, this is the first study to evaluate carboxyterminal propeptide of type I procollagen in sarcoidosis and showed elevated levels in bronchoalveolar lavage fluid. In contrast to the levels of bronchoalveolar lavage fluid aminoterminal propeptide of type III procollagen, levels of carboxyterminal propeptide of type I procollagen did not correlate with serum level of angiotensin converting enzyme and serum interleukin-2 receptor levels, suggesting that carboxyterminal propeptide of type I procollagen may be less suitable disease marker in sarcoidosis than aminoterminal propeptide of type III procollagen. However, the role of carboxyterminal propeptide of type I procollagen as an indicator of fibrogenesis must be further studied.

Analytical, physiologic, and clinical validation of a radioimmunoassay for measurement of procollagen type III amino terminal propeptide in serum and bronchoalveolar lavage fluid obtained from dogs

“…The radioimmunoassay used is very sensitive and precise for measurement of PIIINP in many human biological fluids including serum 9 and BALF. 22 The results of the present study indicated that the assay has good sensitivity, linearity, and reproducibility and acceptable accuracy for measurement of PIIINP in canine serum. Good cross-reactivity between human and canine PIIINP could be expected, given that collagen synthesis and metabolism are known to be well preserved throughout many mammalian species.…”

“…17 Serum and urinary PIIINP concentrations have been studied in humans with various renal diseases 18,19 as well as in patients after renal transplantation 20 and have been shown to correlate with the extent of organ fibrosis. In interstitial pulmonary conditions including pulmonary fibrosis, 5 acute respiratory distress syndrome 21 and sarcoidosis, 22 PIIINP concentrations in both serum and BALF are significantly increased, compared with values in samples from healthy individuals.…”

Serum concentrations of PIIINP aminopeptide in dogs with liver fibrosis

“…In human medicine, numerous studies have been performed to assess the utility of PIIINP in the diagnostics of fibrosis. They revealed Serum concentrations of PIIINP...that this parameter may be useful in the diagnosis of idiopathic pulmonary fibrosis (Norris et al 2005), obstructive pulmonary disease (Harju et al 2010), sarcoidosis, (Lammi et al 1997) and the respiratory distress syndrome (Meduri et al 1998). In humans, PIIINP has also been found to be associated with the myocardial fraction of type III collagen and may be used as a marker of myocardial fibrosis (Izawa at al.…”

Localization of precursor proteins and mRNA of type I and III collagens in usual interstitial pneumonia and sarcoidosis

“…In experimental lung granulomatous inflammation and in human lung sarcoidosis collagen type I can be detected predominantly at the periphery of granulomas, whereas procollagen type I appears to be present within the granulomas (Roman et al 1995). In studies from our laboratory, the concentrations of the aminoterminal propeptide of type III procollagen (PIIINP) and carboxyterminal propeptide of type I procollagen (PICP) were increased in the broncho-alveolar lavage fluid (BALF) and epithelial lining fluid (ELF) of patients with sarcoidosis (Lammi et al 1997) and idiopathic pulmonary fibrosis (i.e. UIP) (Lammi et al 1999).…”