Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients

Abstract Background: Psoriasis is a common chronic inflammatory skin disease associated with the overproduction of interleukin-17A. It has been reported that psoriasis patients had an increased risk of cardiovascular diseases. Ixekizumab is a humanized IgG4-κ monoclonal antibody which has shown efficacy in psoriasis patients. Although the pathogenesis in psoriasis and cardiovascular diseases have a remarkable resemblance, the underlying mechanism of two diseases and the possibility of IL-17A monoclonal antibody in the amelioration of cardiovascular comorbidities remains unclear.Methods: Serum samples of two study cohorts including 117 individuals were analyzed using high throughput UHPLC-MS platform. Non-target metabolic profiling analysis was firstly conducted between healthy people, psoriasis patients and Ixekizumab treated patients in study cohort 1. The second study cohort was additionally recruited to validate the correlation of the identified metabolites and cardiovascular diseases. Results: A total of 43 differential metabolites including lysophospholipids, acyl-carnitines and dicarboxylic acids were accurately identified in study cohort 1, which showed impaired lipids metabolism in psoriasis patients. Results of the study cohort 2 largely conform to the previous observations in study cohort 1. Moreover, all identified LPCs levels were higher in psoriasis patients with coronary heart diseases compared with psoriasis patients. It was worth noting that most of these lipidic changes were ameliorated after receiving Ixekizumab treatment.Conclusion: In this non-target metabolic analysis, we found the treatment of IL-17A monoclonal antibody not only can ameliorate the lesions of psoriasis, but also restore the dysregulated lipids metabolism to normal in psoriasis patients. Considering dysregulated lipids metabolism has been regarded as the critical factor in cardiovascular diseases, the recovery of lipidic metabolites in psoriasis patients indicated that IL-17A mAb might have the potential protective effect on cardiovascular comorbidities.