Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients.
Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients.
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代谢分析揭示白细胞介素 17A 单克隆抗体治疗可改善脂质代谢，并有可能降低银屑病患者的心血管风险
DOI：
10.1186/s12944-021-01441-9
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发表时间：
2021-02-18
影响因子：
4.5
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Cao H;Su S;Yang Q;Le Y;Chen L;Hu M;Guo X;Zheng J;Li X;Yu Y
背景银屑病是一种常见的慢性炎症性皮肤病，与白介素 17A (IL-17A) 过度产生有关。 IL-17A 单克隆抗体 (mAb) 已在银屑病患者中显示出临床疗效。尽管已发现一系列不同的重叠机制建立了银屑病和心血管疾病之间的联系，但两类疾病的潜在机制以及 IL-17A mAb 在改善心血管合并症中的潜在功效仍不清楚。 方法使用高通量 UHPLC-MS 平台对来自两个研究队列（包括 117 名个体）的血清样本进行分析。首先对研究队列 1 中 28 名健康个体和 28 名银屑病患者接受 ixekizumab 治疗 12 周前后的样本进行非靶向代谢谱分析。另外招募研究队列 2 来验证已识别代谢物与心血管疾病的相关性。结果在研究队列中准确鉴定了总共 43 种差异代谢物，包括溶血磷脂、游离脂肪酸、酰基肉碱和二羧酸1、分析显示银屑病患者脂质代谢受损。与健康个体相比，银屑病患者的溶血磷脂酰胆碱、溶血磷脂酰肌醇、溶血磷脂酸和游离脂肪酸水平较高，而酰基肉碱和二羧酸水平较低。确定的二羧酸水平与银屑病面积和严重程度指数（PASI）评分呈负相关（P<0.05）。研究队列2的结果与研究队列1的结果基本一致。此外，患有冠心病的银屑病患者中所有已鉴定的溶血磷脂酰胆碱的水平均高于不患有冠心病的银屑病患者。值得注意的是，大部分脂质变化可通过 ixekizumab 治疗得到改善。 结论 这种非靶向代谢组学分析的结果表明，IL-17A mAb 治疗不仅可以改善银屑病病变，还可以将银屑病患者失调的脂质代谢恢复到正常水平。考虑到脂质代谢失调被认为是心血管疾病的关键因素，银屑病患者脂质代谢物的恢复表明IL-17A mAb可能对心血管合并症具有潜在的保护作用。
BackgroundPsoriasis 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.MethodsSerum 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.ResultsA 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.ConclusionThe 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.
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大规模代谢组分析确定了出现冠心病的新生物标志物。
影响因子：
4.5
作者：
Ganna A;Salihovic S;Sundström J;Broeckling CD;Hedman AK;Magnusson PK;Pedersen NL;Larsson A;Siegbahn A;Zilmer M;Prenni J;Arnlöv J;Lind L;Fall T;Ingelsson E
通讯作者：
Ingelsson E
影响因子：
4.4
作者：
Chiurchiu, Valerio;Lanuti, Mirko;Maccarrone, Mauro
通讯作者：
Maccarrone, Mauro
影响因子：
158.5
作者：
Gordon, K. B.;Blauvelt, A.;Leonardi, C. L.
通讯作者：
Leonardi, C. L.
影响因子：
3.7
作者：
Carneiro AB;Iaciura BM;Nohara LL;Lopes CD;Veas EM;Mariano VS;Bozza PT;Lopes UG;Atella GC;Almeida IC;Silva-Neto MA
通讯作者：
Silva-Neto MA
影响因子：
4.3
作者：
Aiyar, Nambi;Disa, Jyoti;Douglas, Stephen A.
通讯作者：
Douglas, Stephen A.