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. 2018;35(1):5-15.
doi: 10.36141/svdld.v35i1.5834. Epub 2018 Apr 28.

Identification of apolipoprotein A-I in BALF as a biomarker of sarcoidosis

Yoshihisa Nukui  1 , Yasunari Miyazaki  1 , Kozo Suhara  1 , Tsukasa Okamoto  1 , Haruhiko Furusawa  1 , Naohiko Inase  1
Affiliations

Identification of apolipoprotein A-I in BALF as a biomarker of sarcoidosis

Yoshihisa Nukui et al. Sarcoidosis Vasc Diffuse Lung Dis. 2018.

Abstract

Background: Sarcoidosis goes into remission in two-thirds of patients with sarcoidosis, but about 20 % of patients develop pulmonary fibrosis. The mechanisms of pulmonary fibrosis in sarcoidosis and differences in pathogenesis between clinical stages are still unclear. Objectives: The aim of this study was investigating proteins associated with clinical stages by comparing bronchoalveolar lavage fluid (BALF) protein between stage I and stage IV using proteome analysis. Methods: Proteomic differences in BALF were compared between stage I and stage IV by examining BALF from 8 stage I patients and 5 stage IV patients by two-dimensional gel electrophoresis and mass spectrometry. Results: In individual comparisons of BALF samples, the levels of apolipoprotein (Apo) A-I fragment, fibrinogen γ chain, calcyphosine, complement C3, and surfactant protein A were significantly higher in stage I than in stage IV. In contrast, none of the proteins examined significantly higher in stage IV than in stage I. To confirm the results of Apo A-I in the BALF proteome, we performed enzyme-linked immunosorbent assay (ELISA) in a larger group. The concentration of BALF Apo A-I was significantly higher in stage I patients than in stage IV patients (0.70 [0.13-0.89] vs. 0.15 [0.08-0.21] ng/μg protein, p=0.003). Conclusion: The involvement of BALF Apo A-I in sarcoidosis may differ between stage I and stage IV. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 5-15).

Keywords: apolipoprotein A-I; bronchoalveolar lavage fluid; interstitial pneumonia; proteomics; sarcoidosis.

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Figures

Fig. 1.
Fig. 1.
Two-Dimensional Electrophoresis (2-DE) of BALF from sarcoidosis patient with stage I (A) stained by SYPRO-Ruby. Numbers indicate proteins, as listed in Table 2. Representative 2-DE patterns of BALF from stage I (B) and stage IV (C). The square area is magnified in Fig. 1D. Apo A-I fragments (spot“ a ” - “ c ”) and Apo A-I (spot“ d ” - “ e ”) were shown as five spots
Fig. 2.
Fig. 2.
The normalized BALF Apo A-I concentration with total protein in sarcoidosis with stage I (Sar. I), sarcoidosis with stage IV (Sar. IV), rheumatoid arthritis-associated interstitial lung disease with organizing pneumonia pattern (RA-ILD OP), rheumatoid arthritis-associated interstitial lung disease with usual interstitial pneumonia pattern (RA-ILD UIP), idiopathic pulmonary fibrosis (IPF), and healthy volunteers (HV). * p<0.05
Fig. 3.
Fig. 3.
Correlation between normalized concentration of BALF Apo A-I and the percentage of lymphocytes in BALF in stage I sarcoidosis
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