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Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease involving extensive tissue inflammation, damage, and liver dysfunction,and it has become a serious occupational health hazard.The aim of this study was to develop potential serum biomarkers for OMLDT using a fast and efficient method of high-performance liquid chromatography (HPLC) coupled to MALDI-TOF/TOF-MS.We collected fasting blood samples from patients with OMLDT (n =18) and healthy volunteers (n =33) to explore serum peptidome patterns.Blood proteins were purified with magnetic bead-based weak cation exchange chromatography (MB-WCX) and analyzed with MALDI-TOF-MS.ClinProTools and supervised neural network (SNN) algorithms were used on the training and testing data sets to establish classification models.Thirty protein/peptide peaks were significantly different between the two groups and were selected as potential biomarkers of OMLDT patients;The SNN algorithm utilized three peaks (m/z 2106.3, 2134.5,and 3263.67 Da) to separate the OMLDT patients from the healthy controls, with a cross validation of 94.44% and a recognition capability of 100%.The test sensitivity was 95.5%, and the test specificity was 73.8%.HPLC-TOF/TOF-MS identified four proteins that may play a role in the pathology of OMLDT: ATP-binding cassette transporter, mutant beta-actin, a fragment of albumin, and cationic trypsinogen.Specific proteomic fingerprints in the sera of OMLDT patients could be used to identify OMLDT cases with high specificity and sensitivity.The HPLC-TOF/TOF-MS approach will be of great value for exploring potential biomarkers and can be readily applied to clinical studies.