Increased serum VDBP as a risk predictor for steroid resistance in asthma patients.

BACKGROUND: Asthmatic symptoms usually can be controlled with corticosteroids, but partly asthmatic patients do not respond to corticosteroids, steroid resistance (SR) play a significant role in the poorly responding. However, no approach can accurately predict steroid responsiveness in asthma patients, so prediction of SR with noninvasive means has become a critical issue.

OBJECTIVE: The aim of this study was to evaluate the difference in serum proteomes between steroid-sensitive asthma (SSA) and steroid-resistant asthma (SRA) patients and identify potential biomarkers for the prediction of SR in asthma patients.

METHODS: We performed a proteomic approach of fluorescence-based difference gel electrophoresis (DIGE) and mass spectrometry to identify biomarkers in the serum obtained from SRA and SSA patients (n = 6 in each group). The interesting biomarker was further studied using western blot and enzyme-linked immunosorbent assays (ELISA).

RESULTS: Seven differentially expressed proteins between SSA and SRA group were identified. Among them, vitamin D-binding protein (VDBP) attracted our further attention as the greatest changed protein. Serum VDBP was significantly up-regulated in SRA group compared with SSA group, and the differential expression was confirmed with western blot analysis. The ELISA data showed the serum level of VDBP was significantly higher in SRA group than that in SSA and control group (496.50 ± 204.62 vs. 279.73 ± 163.65, 241.93 ± 98.58 μg/ml, respectively, p < 0.01). Correlation analysis indicated serum VDBP was positively correlated with neutrophils% and monocytes% (p < 0.05), but inversely correlate with serum 25OHD (p < 0.05). Regression analysis showed increased serum VDBP was a risk predictor of SRA, and serum 25OHD was an independent influential factor of serum VDBP. Using the receiver operating characteristic curve, we determined the area under the curve (AUC) of VDBP was 0.792, and the optimal serum cutoff value of VDBP was 355.8 μg/ml, which can discriminate SRA from asthma patients with 65.2% sensitivity and 83.7% specificity.

CONCLUSIONS: This study provides a novel overview of the difference in serum proteomes of SSA and SRA. We suppose serum VDBP may serve as a useful biomarker for predicting SR in asthma patients, and may participate in the pathogenesis of SRA.