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

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease associated with overproduction of interleukin-17A (IL-17A). IL-17A monoclonal antibodies (mAbs) have shown clinical efficacy in psoriasis patients. Although a series of different overlapping mechanisms have been found to establish a link between psoriasis and cardiovascular diseases, the underlying mechanisms of the two types of diseases and the potential efficacy of IL-17A mAbs in amelioration of cardiovascular comorbidities remain unclear. METHODS: Serum samples from two study cohorts including 117 individuals were analyzed using a high-throughput UHPLC-MS platform. Non-targeted metabolic profiling analysis was first conducted with samples from 28 healthy individuals and from 28 psoriasis patients before and after 12-weeks of ixekizumab treatment in study cohort 1. Study cohort 2 was additionally recruited to validate the correlations of the identified metabolites with cardiovascular diseases. RESULTS: A total of 43 differential metabolites, including lysophospholipids, free fatty acids, acylcarnitines and dicarboxylic acids, were accurately identified in study cohort 1, and the analysis showed that lipid metabolism was impaired in psoriasis patients. Compared with healthy individuals, psoriasis patients had higher levels of lysophosphatidylcholines, lysophosphatidylinositols, lysophosphatidic acids and free fatty acids, but lower levels of acylcarnitines and dicarboxylic acids. The identified dicarboxylic acid levels were inversely correlated with psoriasis area and severity index (PASI) scores (P < 0.05). The results for study cohort 2 were largely consistent with the results for study cohort 1. Moreover, the levels of all identified lysophosphatidylcholines were higher in psoriasis patients with coronary heart diseases than in psoriasis without coronary heart disease. Notably, most of these lipidic changes were ameliorated by ixekizumab treatment. CONCLUSION: The results of this non-targeted metabolomic analysis indicate that treatment with IL-17A mAbs can not only ameliorate psoriasis lesions but also restore dysregulated lipid metabolism to normal levels in psoriasis patients. Considering that dysregulated lipid metabolism has been regarded as the critical factor in cardiovascular diseases, the recovery of lipid metabolites in psoriasis patients indicates that IL-17A mAbs might have the potential protective effects against cardiovascular comorbidities.

Online preconcentration of recombinant Arg-Gly-Asp-hirudin using dynamic pH junction for analysis in human urine samples by capillary electrophoresis-mass spectrometry.

A sensitive and effort-saving method was established and validated for the quantitative determination of recombinant Arg-Gly-Asp-hirudin (rRGD-hirudin) in human urine samples. The assay was performed on a uncoated fused silica capillary of 70 cm x 50 microm I.D. and a positive voltage of 30 kV was applied. The sample was injected under pressure of 50 mbar for 300 s and the temperature of capillary was kept 25 degrees C. Sheath liquid consisting of 30% methanol and 70% of 0.1% formic acid aqueous solution flowing at 7 microL/min was supplied to the CE-electrospray interface. Utilizing the dynamic pH junction technique, a lower limit of quantitation of approximately 35 nM was achieved (concentration coefficiency was about 100-fold) without complex sample preprocessing procedure. CE-MS conditions and parameters were also optimized to obtain better performance. The method has been successfully applied in clinical research of rRGD-hirudin.

A development of LC-MS method combining ultrafiltration and lyophilization for determination of r-RGD-Hirudin in human serum.

A reliable and validated LC-MS method was established for determination of r-RGD-Hirudin in human serum. Ultrafiltration was used instead of liquid-liquid extraction or solid phase extraction for water solubility drug r-RGD-Hirudin extraction. Freeze drying was used for concentration. The experiment conditions, including pre-processing procedure and LC-MS, have been investigated and optimized. Comparing with reported assays, the current method showed significant improvement in specificity, linearity, precision and sensitivity. This method has been successfully applied in clinical research of r-RGD-Hirudin.