Serum ferritin and transferrin levels as serologic markers of methylene diphenyl diisocyanate–induced occupational asthma

Background

Although methylene diphenyl diisocyanate (MDI) may induce occupational asthma in the workplace, the pathogenic mechanisms are unclear.

Objectives

By using bronchoalveolar lavage fluid, we sought to identify proteins that were differentially expressed between subjects with MDI-induced occupational asthma (MDI-OA) and asymptomatic exposed controls (AECs).

Methods

To find proteins that were differentially expressed between the MDI-OA and AEC groups, 2-dimensional electrophoresis was performed by using bronchoalveolar lavage fluid obtained from subjects after MDI-specific inhalation challenge. The selected protein spots were then identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The clinical relevance of the differentially expressed spots was compared by ELISA using sera from the MDI-OA/eosinophilic bronchitis, AEC, and unexposed healthy control groups. Receiver operating characteristic curves were then plotted, and the sensitivity and specificity were determined.

Results

Twenty-three protein spots were identified that distinguished the subjects with MDI-OA from those in the AEC group. Among them, ferritin expression was downregulated whereas transferrin expression was upregulated in subjects with MDI-OA compared with AEC; these results were validated by ELISA using sera from the MDI-OA/EB and AEC groups. To identify subjects with MDI-OA, the optimal serum cutoff levels were 69.84 ng/mL for ferritin and 2.48 μg/mL for transferrin. When these 2 parameters were combined, the sensitivity was 71.43% and the specificity was 85.71%.

Conclusion

Serum ferritin and transferrin levels are associated with the phenotype of MDI-OA.

Key words: MDI, occupational asthma, ferritin, transferrin, proteome

Abbreviations used: 2-DE, 2-Dimensional electrophoresis, AEC, Asymptomatic exposed control, ANCOVA, Analysis of covariance, ARDS, Acute respiratory distress syndrome, AUC, Area under the curve, BALF, Bronchoalveolar lavage fluid, DBP, Vitamin D–binding protein precursor, EB, Eosinophilic bronchitis, MALDI-TOF/TOF MS, Matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry, MDI, Methylene diisocyanate, MDI-EB, Methylene diisocyanate–induced eosinophilic bronchitis, MDI-OA, Methylene diisocyanate–induced occupational asthma, MS, Mass spectrometry, NC, Nonatopic healthy control, ROC, Receiver operating characteristic, TDI, Toluene diisocyanate, TDI-OA, Toluene diisocyanate–induced occupational asthma, WRRS, Work-related lower respiratory symptom