Integrated metabolomics and lipidomics study of patients with atopic dermatitis in response to dupilumab

Lishan Zhang; Xueyi Wen; Yibo Hou; Yongshi Yang; Wei Song; Yueping Zeng; Jinlyu Sun

doi:10.3389/fimmu.2022.1002536

Integrated metabolomics and lipidomics study of patients with atopic dermatitis in response to dupilumab

Front Immunol. 2022 Oct 20:13:1002536. doi: 10.3389/fimmu.2022.1002536. eCollection 2022.

Authors

Lishan Zhang^{1

2}, Xueyi Wen^{1

2}, Yibo Hou^{1

2}, Yongshi Yang^{1

2}, Wei Song³, Yueping Zeng⁴, Jinlyu Sun^{1

2}

Affiliations

¹ Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Allergy Department, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Medical Science Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
⁴ Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China.

Abstract

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 investigated 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.

Keywords: atopic dermatitis; different response; dupilumab; lipidomics; metabolomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dermatitis, Atopic* / drug therapy
Humans
Lipidomics
Metabolomics
Severity of Illness Index
Treatment Outcome

Substances

dupilumab