Serum lipidomic study of long-chain fatty acids in psoriasis patients prior to and after anti-IL-17A monoclonal antibody treatment by quantitative GC‒MS analysis with in situ extraction

• Published in: Lipids in health and disease Vol. 23; no. 1; pp. 6 - 15
• Main Authors: Guo, XiaoYu, Zhou, Jianglu, Yu, Hong, Cao, Han, Li, Xia, Hu, Qing, Yu, YunQiu
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08-01-2024; BioMed Central; BMC
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Development and progression; Drug therapy; Ethics; Fatty acid metabolism; Fatty Acids; Fatty Acids, Monounsaturated; Gas chromatography; Gas Chromatography-Mass Spectrometry; Health aspects; Humans; Imiquimod; Inflammation; Interleukin-17 - genetics; Laboratory animals; Lipidomics; Long-chain fatty acids; Lymphocytes T; Mass spectroscopy; Metabolism; Metabolites; Methods; Mice; Monoclonal antibodies; Pathogenesis; Patients; Pharmacy; Polyunsaturated fatty acids; Psoriasis; Psoriasis - drug therapy; Skin diseases; Skin lesions; T cell receptors; Targeted metabolomics; China; St Louis Missouri; United States > US; Targeted metabolomics; Psoriasis; Long-chain fatty acids; Gas chromatography‒mass spectrometry
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-023-01999-6

Long-chain fatty acids (LCFAs) are involved in regulating multiple physiological processes as signalling molecules. Gas chromatography-mass spectrometry (GC-MS) is widely used to quantify LCFAs. However, current quantitative methods for LCFAs using GC-MS have demonstrated complicated issues. Psoriasis is a chronic inflammatory skin disease, and its pathogenesis may be related to the overproduction of interleukin-17A (IL-17A). Clinical efficacy of anti-IL-17A monoclonal antibody (mAb) treatment in psoriasis patients has been demonstrated. Recent studies suggest that LCFAs play varying roles in the pathogenesis of psoriasis. However, more comprehensive research is needed to illuminate the mechanism of LCFAs in psoriasis.
The established in situ derivatization method for analysing LCFAs with a GC-MS platform was utilized to conduct serum lipidomics analysis of healthy volunteers and psoriasis patients receiving pretherapy and posttreatment with of anti-IL-17A mAb. Imiquimod (IMQ)-treated wild type (WT) and T-cell receptor delta chain knock-out (Tcrd
) mice were used to investigate the correlation between IL-17A and abnormal changes in LCFAs in psoriasis patients.
A rapid and sensitive in situ extraction derivatization method for quantifying LCFAs using GC-MS was established. Serum lipidomic results showed that psoriasis patients had higher levels of saturated fatty acids (SFAs) and ω-6 polyunsaturated fatty acids (PUFAs) but lower levels of monounsaturated fatty acids (MUFAs) and ω-3 PUFAs than healthy individuals, indicating impaired serum LCFA metabolism. Anti-IL-17A mAb treatment affected most of these LCFA changes. Analysis of LCFAs in IMQ-treated mice showed that LCFAs increased in the serum of WT mice, while there were no significant changes in the Tcrd
mice. SFAs increased in IMQ-treated WT mice, while MUFAs showed the opposite trend, and PUFAs did not change significantly.
This study presented a dependable method for quantifying LCFAs that enhanced sensitivity and reduced analysis time. The lipidomic analysis results showed that anti-IL-17A mAb not only ameliorated skin lesions in psoriasis patients but also affected abnormal LCFAs metabolism. Furthermore, the study indicated a potential correlation between IL-17A and abnormal LCFA metabolism in psoriasis patients, which was supported by the alterations in serum LCFAs observed in IMQ-treated WT and Tcrd
mice.