{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002302","ANALYSIS_ID":"AN003762","VERSION":"1","CREATED_ON":"October 3, 2022, 9:13 am"},

"PROJECT":{"PROJECT_TITLE":"Integrated metabolomics and lipidomics study of patients with atopic dermatitis in response to dupilumab","PROJECT_SUMMARY":"Background: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Dupilumab, a monoclonal antibody that targets the interleukin (IL)-4 and IL-13 receptors, has been widely used in AD because of its efficacy. However, metabolic changes occurring in patients with AD in response to dupilumab remains unknown. In this study, we integrated metabolomics and lipidomics analyses with clinical data to explore potential metabolic alterations associated with dupilumab therapeutic efficacy. In addition, we investigate whether the development of treatment side effects was linked to the dysregulation of metabolic pathways. Methods: A total of 33 patients with AD were included in the current study, with serum samples collected before and after treatment with dupilumab. Comprehensive metabolomic and lipidomic analyses have previously been developed to identify serum metabolites (including lipids) that vary among treatment groups. An orthogonal partial least squares discriminant analysis model was established to screen for differential metabolites and metabolites with variable importance in projection > 1 and p < 0.05 were considered potential metabolic biomarkers. MetaboAnalyst 5.0 was used to identify related metabolic pathways. Patients were further classified into two groups, well responders (n = 19) and poor responders (n = 14), to identify differential metabolites between the two groups. Results: The results revealed significant changes in serum metabolites before and after 16 weeks of dupilumab treatment. Variations in the metabolic profile were more significant in the well-responder group than in the poor-responder group. Pathway enrichment analysis revealed that differential metabolites derived from the well-responder group were mainly involved in glycerophospholipid metabolism, valine, leucine and isoleucine biosynthesis, the citrate cycle, arachidonic acid metabolism, pyrimidine metabolism, and sphingolipid metabolism. Conclusion: Serum metabolic profiles of patients with AD varied significantly after treatment with dupilumab. Differential metabolites and their related metabolic pathways may provide clues for understanding the effects of dupilumab on patient metabolism.","INSTITUTE":"Peking Union Medical College Hospital, Chinese Academy of Medical Sciences","LAST_NAME":"Zhang","FIRST_NAME":"Lishan","ADDRESS":"No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.","EMAIL":"429647356@qq.com","PHONE":"+86-18612636397"},

"STUDY":{"STUDY_TITLE":"Integrated metabolomics and lipidomics study of patients with atopic dermatitis in response to dupilumab","STUDY_SUMMARY":"Background: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Dupilumab, a monoclonal antibody that targets the interleukin (IL)-4 and IL-13 receptors, has been widely used in AD because of its efficacy. However, metabolic changes occurring in patients with AD in response to dupilumab remains unknown. In this study, we integrated metabolomics and lipidomics analyses with clinical data to explore potential metabolic alterations associated with dupilumab therapeutic efficacy. In addition, we investigate whether the development of treatment side effects was linked to the dysregulation of metabolic pathways. Methods: A total of 33 patients with AD were included in the current study, with serum samples collected before and after treatment with dupilumab. Comprehensive metabolomic and lipidomic analyses have previously been developed to identify serum metabolites (including lipids) that vary among treatment groups. An orthogonal partial least squares discriminant analysis model was established to screen for differential metabolites and metabolites with variable importance in projection > 1 and p < 0.05 were considered potential metabolic biomarkers. MetaboAnalyst 5.0 was used to identify related metabolic pathways. Patients were further classified into two groups, well responders (n = 19) and poor responders (n = 14), to identify differential metabolites between the two groups. Results: The results revealed significant changes in serum metabolites before and after 16 weeks of dupilumab treatment. Variations in the metabolic profile were more significant in the well-responder group than in the poor-responder group. Pathway enrichment analysis revealed that differential metabolites derived from the well-responder group were mainly involved in glycerophospholipid metabolism, valine, leucine and isoleucine biosynthesis, the citrate cycle, arachidonic acid metabolism, pyrimidine metabolism, and sphingolipid metabolism. Conclusion: Serum metabolic profiles of patients with AD varied significantly after treatment with dupilumab. Differential metabolites and their related metabolic pathways may provide clues for understanding the effects of dupilumab on patient metabolism.","INSTITUTE":"Peking Union Medical College Hospital, Chinese Academy of Medical Sciences","LAST_NAME":"Zhang","FIRST_NAME":"Lishan","ADDRESS":"No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.","EMAIL":"429647356@qq.com","PHONE":"+86-18612636397"},

"SUBJECT":{"SUBJECT_TYPE":"Human","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606","AGE_OR_AGE_RANGE":">=18","GENDER":"Male and female","HUMAN_RACE":"Chinese","HUMAN_ETHNICITY":"Han","HUMAN_TRIAL_TYPE":"observational study","HUMAN_MEDICATIONS":"Dupilumab","HUMAN_INCLUSION_CRITERIA":"1.Age ≥ 18 years of age 2.Dermatologist diagnosis of moderate to severe AD, EASI≥16 at baseline 3.Eligible to receive dupilumab therapy for AD in accordance with the guidelines. Patients who are eligible were treated with a fixed schedule of 300mg dupilumab in 2-week intervals. Patients who did not achieve 16-week therapy were excluded. 4.During the whole treatment process, the requirements for diet and exercise are roughly the same as before treatment, so as to keep the body healthy and balanced 5.A 30-day washout period of systemic medications preceded treatment","HUMAN_EXCLUSION_CRITERIA":"1Evidence of other skin diseases except for AD at baseline 2.Pregnancy or breast feeding, 3.Patients with permanent severe diseases, especially those affecting the immune system, except asthma 4.Patients with severe mental illness 5.Evidence of chronic metabolic disease, including Obesity, diabetes, fatty liver, osteoporosis, atherosclerotic cardiovascular and cerebrovascular diseases, and metabolic-related cancers (breast, colorectal, pancreatic, colon, and prostate cancer). 6.Application of other systemic medications during treatment"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"QC01",
"Factors":{"Treatment":"Control"},
"Additional sample data":{"RAW_FILE_NAME":"QC01.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"QC02",
"Factors":{"Treatment":"Control"},
"Additional sample data":{"RAW_FILE_NAME":"QC02.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"QC03",
"Factors":{"Treatment":"Control"},
"Additional sample data":{"RAW_FILE_NAME":"QC03.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"QC04",
"Factors":{"Treatment":"Control"},
"Additional sample data":{"RAW_FILE_NAME":"QC04.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"QC05",
"Factors":{"Treatment":"Control"},
"Additional sample data":{"RAW_FILE_NAME":"QC05.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"QC06",
"Factors":{"Treatment":"Control"},
"Additional sample data":{"RAW_FILE_NAME":"QC06.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"QC07",
"Factors":{"Treatment":"Control"},
"Additional sample data":{"RAW_FILE_NAME":"QC07.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A1",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A1.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A2",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A2.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A3",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A3.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A4",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A4.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A5",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A5.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A6",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A6.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A7",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A7.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A8",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A8.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A9",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A9.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A10",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A10.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A11",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A11.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A12",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A12.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A13",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A13.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A14",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A14.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A15",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A15.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A16",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A16.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A17",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A17.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A18",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A18.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A19",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A19.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A20",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A20.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A21",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A21.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A22",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A22.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A23",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A23.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A24",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A24.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A25",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A25.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A26",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A26.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A27",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A27.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A28",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A28.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A29",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A29.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A30",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A30.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A31",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A31.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A32",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A32.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"A33",
"Factors":{"Treatment":"Before dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"A33.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B1",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B1.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B2",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B2.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B3",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B3.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B4",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B4.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B5",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B5.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B6",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B6.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B7",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B7.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B8",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B8.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B9",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B9.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B10",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B10.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B11",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B11.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B12",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B12.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B13",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B13.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B14",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B14.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B15",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B15.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B16",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B16.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B17",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B17.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B18",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B18.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B19",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B19.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B20",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B20.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B21",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B21.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B22",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B22.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B23",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B23.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B24",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B24.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B25",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B25.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B26",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B26.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B27",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B27.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B28",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B28.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B29",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B29.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B30",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B30.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B31",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B31.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B32",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B32.mzXML"}
},
{
"Subject ID":"-",
"Sample ID":"B33",
"Factors":{"Treatment":"After dupilumab treatment"},
"Additional sample data":{"RAW_FILE_NAME":"B33.mzXML"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"We recruited 33 patients diagnosed with moderate to severe atopic dermatitis at the dermatology outpatient clinic of the Peking Union Medical College Hospital from March 2021 to February 2022. Serum samples from each participant were obtained after overnight fasting at the outpatient clinic of the Peking Union Medical College Hospital and were collected before and after 16 weeks of dupilumab treatment. The serum samples were immediately frozen at -80°C until analysis.","SAMPLE_TYPE":"Blood (serum)"},

"TREATMENT":{"TREATMENT_SUMMARY":"All the enrolled participants were treated with dupilumab for 16 weeks.","TREATMENT":"Biologics Formulation","TREATMENT_ROUTE":"in 2-week intervals","TREATMENT_DOSE":"300mg dupilumab","TREATMENT_DOSEVOLUME":"300mg dupilumab"},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"100 μL of sample was transferred to an EP tube. After the addition of 400 μL of extract solution (acetonitrile: methanol = 1: 1, containing isotopically-labelled internal standard mixture), the samples were vortexed for 30 s, sonicated for 10 min in ice-water bath, and incubated for 1 h at -40 ℃ to precipitate proteins. Then the sample was centrifuged at 12000 rpm(RCF=13800(×g),R= 8.6cm) for 15 min at 4 ℃. The resulting supernatant was transferred to a fresh glass vial for analysis. The quality control (QC) sample was prepared by mixing an equal aliquot of the supernatants from all of the samples."},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"HILIC","INSTRUMENT_NAME":"Thermo Vanquish","COLUMN_NAME":"Waters Acquity BEH C8 (100 x 2.1mm, 1.7um)"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"Thermo Q Exactive HF-X Orbitrap","INSTRUMENT_TYPE":"Orbitrap","MS_TYPE":"ESI","ION_MODE":"NEGATIVE","MS_COMMENTS":"-","MS_RESULTS_FILE":"ST002302_AN003762_Results.txt UNITS:Peak area Has m/z:Yes Has RT:Yes RT units:Minutes"}

}