Altered Serum Phospholipids in Atopic Dermatitis and Association with Clinical Status

Sakai, Takashi; Herrmann, Nadine; Maintz, Laura; Nümm, Tim Joachim; Welchowski, Thomas; Claus, Ralf A.; Gräler, Markus H.; Bieber, Thomas

doi:10.1016/j.xjidi.2021.100092

Cited by 8 publications

(11 citation statements)

References 35 publications

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“…Therefore, we speculate that serum lipid metabolism may not only play an important role in the development of AD but also play a role in the biological response to treatment in patients with AD. Our results showed that lipid differential metabolites were dominated by PC, which are similar to many serum lipidomic studies on AD ( 19 – 21 ). However, these studies aimed to investigate the differential metabolic profile between patients with AD and healthy people, whereas in this study we included patients who received dupilumab for treatment to explore the change in the global metabolomics profile after therapy.…”

Section: Discussionsupporting

confidence: 88%

“…Increasing evidence shows that GP metabolism plays an important role in inflammationassociated skin diseases (24). We also found that for PCs, the most abundant class of lipids (25), several studies have (19). These variants of PC were found to be up-regulated in patients with AD in Sakai's study, whereas our research showed that they were down-regulated after dupilumab treatment.…”

Section: Discussionsupporting

confidence: 45%

“…When integrating the differential metabolites screened from the metabolome and lipidome of all AD patients, we noticed that the most abundant classes were lipid and lipid-like molecules. Previous metabolomics and lipidomics studies have also shown that patients with AD have different lipid profiles than healthy individuals ( 14 , 19 ). Therefore, we speculate that serum lipid metabolism may not only play an important role in the development of AD but also play a role in the biological response to treatment in patients with AD.…”

Section: Discussionmentioning

confidence: 96%

“…However, these studies aimed to investigate the differential metabolic profile between patients with AD and healthy people, whereas in this study we included patients who received dupilumab for treatment to explore the change in the global metabolomics profile after therapy. Sakai et al demonstrated that multiple variants of PC, including PC (32:1) and PC (36:4), were increased in patients with AD compared to healthy controls (19). Meanwhile, our findings suggest that PC (16:0/16:1) and PC (16:0/20:4), also known as PC (32:1) and PC (36:4), respectively, decreased after treatment (Figure 2B).…”

Section: Discussionmentioning

confidence: 99%

“…Sakai et al. demonstrated that multiple variants of PC, including PC (32:1) and PC (36:4), were increased in patients with AD compared to healthy controls ( 19 ). Meanwhile, our findings suggest that PC (16:0/16:1) and PC (16:0/20:4), also known as PC (32:1) and PC (36:4), respectively, decreased after treatment ( Figure 2B ).…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Wen²,

Hou³

et al. 2022

Front. Immunol.

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BackgroundAtopic 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.MethodsA 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.ResultsThe 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.ConclusionSerum 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.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 45%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

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

Zhang

Wen²,

Hou³

et al. 2022

Front. Immunol.

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Atopic Dermatitis and Psoriasis: Similarities and Differences in Metabolism and Microbiome

Chen,

Peng,

Zhu

et al. 2024

Clinic Rev Allerg Immunol

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Immunoglobulin E autoantibodies in atopic dermatitis associate with Type‐2 comorbidities and the atopic march

Kortekaas Krohn,

Badloe,

Herrmann

et al. 2023

Allergy

Self Cite

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BackgroundAutoreactive immunoglobulin E (IgE) antibodies to self‐peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well‐characterized patients with AD and controls (1.2–88.9 years).MethodsAtopic dermatitis patients were sub‐grouped in AD with comorbid Type‐2 diseases (“AD + Type 2”; asthma, allergic rhinitis, food allergy, n = 431) or “solely AD” (n = 115). Also, subjects without AD but with Type‐2 diseases (“atopic controls,” n = 52) and non‐atopic “healthy controls” (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples.ResultsImmunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD‐patients. “AD + Type 2” showed a higher prevalence (16.4%) than “solely AD” (9.6%). “Atopic controls” (9.6%) were comparable with “solely AD” patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with “AD + Type 2”. AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean‐section and diversity of domestic pets.ConclusionsImmunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration.

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Altered Serum Phospholipids in Atopic Dermatitis and Association with Clinical Status

Cited by 8 publications

References 35 publications

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

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

Atopic Dermatitis and Psoriasis: Similarities and Differences in Metabolism and Microbiome

Immunoglobulin E autoantibodies in atopic dermatitis associate with Type‐2 comorbidities and the atopic march

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