Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis

Abstract

Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis. C. Hermans, M. Petrek, V. Kolek, B. Weynand, T. Pieters, M. Lambert, A. Bernard. #ERS Journals Ltd 2001. ABSTRACT: To test the hypothesis that sarcoidosis is associated with an intravascular leakage of lung epithelium secretory proteins, the occurrence and determinants in serum of sarcoid patients of CC16, a small size and readily diffusible lung-specific protein of 16 kDa secreted by bronchiolar Clara cells, was investigated.CC16 was measured by a sensitive latex immunoassay in the serum of 117 patients with established sarcoidosis and of 117 healthy subjects matched for age, sex and smoking status. Stepwise regression analysis was used to identify extrapulmonary variables of CC16 changes in serum. These changes were then compared with biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF) as well as with the number of CC16 immunostaining cells on bronchial or pulmonary biopsy samples.CC16 concentration in serum of sarcoid patients was significantly increased, compared to their matched controls (25.9¡16.2 versus 13.9¡5.2 mg?L -1 ). In nonsmoking patients without significant renal impairment, CC16 in serum increased with the severity of the chest radiograph and computed tomography changes, and was on average 50-100% higher when parenchymal involvement was present. Sarcoid patients had, however, normal levels of CC16 in BALF and an unchanged number of CC16-immunopositive cells in lung biopsy samples, suggesting that an increased secretion of CC16 in the sarcoid lung is very unlikely, and that the elevation of CC16 in sarcoidosis results from an increased intravascular leakage of the protein across the air-blood barrier.The present study suggests that CC16 in serum might provide a useful tool to noninvasively evaluate the damage and increased permeability to proteins of the airblood barrier associated with sarcoidosis.

Proteomics of bronchoalveolar lavage fluid

“…For example, increase of BALF surfactant protein A may result from increase of the synthesis and/or release by secreting cells or by impaired clearance by alveolar macrophages, mucociliary transport, degradation, and absorption into the bloodstream. Increased synthesis and/or release are the most plausible mechanisms explaining BALF SP-A increase in patients with sarcoidosis [65]. The analysis of the BALF proteome may, thus be helpful to quantify the overall molecular changes associated with lung injuries but may also offer the possibility to directly monitor therapeutic interventions.…”

Cord blood Clara cell protein CC16 predicts the development of bronchopulmonary dysplasia

“…If purified CC16 is applied to serum, this assay has a detection limit of 0.5 μg/L and an average analytical recovery of 95%. The intra-assay and inter-assay coefficients of variation range from 5 to 10% [15,16]. The sPLA 2 enzyme activity was measured by the hydrolysis of 2-3 H-linoleyl-phosphatidyl-ethanolamine and was expressed as nmol/mL/h hydrolysis [29].…”

Clara cell secretory protein (CC16) as a peripheral blood biomarker of lung injury in ventilated preterm neonates

“…However, clinical studies have shown that circulating CC16 rises in various pulmonary diseases characterised by increased epithelial permeability, such as acute respiratory distress syndrome [18], idiopathic interstitial pneumonia [26] and sarcoidosis [12], as well as after exposure to environmental air pollutants [6] or fire smoke [5]. On the basis of this evidence, CC16 has been proposed as a potential, non-invasive, peripheral, blood biomarker specific to the lung injury.…”