Levels of the Novel Endogenous Antagonist of Ghrelin Receptor, Liver-Enriched Antimicrobial Peptide-2, in Patients with Rheumatoid Arthritis
Levels of the Novel Endogenous Antagonist of Ghrelin Receptor, Liver-Enriched Antimicrobial Peptide-2, in Patients with Rheumatoid Arthritis
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DOI：
10.3390/nu12041006
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发表时间：
2020-04-01
期刊：
影响因子：
5.9
通讯作者：
Gualillo, Oreste
中科院分区：
文献类型：
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作者：
Francisco, Vera;Tovar, Sulay;Gualillo, Oreste
类风湿关节炎（RA）是一种与恶病质相关的使人衰弱的慢性炎症性自身免疫性疾病。肠道激素生长素释放肽的替代疗法被认为是治疗 RA 代谢和炎症并发症的潜在对策。最近发现肝脏表达的抗菌肽 2 (LEAP2) 作为生长素释放肽受体的内源性反向激动剂/拮抗剂，使得开发更合理的药理学方法成为可能。这项工作旨在评估一组 RA 患者与健康个体的血清 LEAP2 水平，并确定其与炎症参数的相关性。通过商业 ELISA 试剂盒测定 LEAP2 水平，使用免疫比浊法评估血浆 C 反应蛋白 (CRP) 水平，并通过 XMap 多重测定法测量炎症介质（即 IL-6、IL-8、IL-1 beta、MIP1 α、MCP1 和 LCN2）的血清水平。与对照受试者 (n = 26) 相比，RA 患者 (n = 101) 的 LEAP2 血清水平显着升高。此外，LEAP2 水平与 CRP 和炎症细胞因子显着相关，但与 BMI 无关。这些数据揭示了 LEAP2 作为一种新的潜在 RA 生物标志物，并表明对 LEAP2 水平的药理学控制是治疗 ghrelin 水平改变的疾病（例如类风湿性恶病质）的新方法。
Rheumatoid arthritis (RA) is a debilitating, chronic, inflammatory, autoimmune disease associated with cachexia. The substitutive therapy of gut hormone ghrelin has been pointed at as a potential countermeasure for the management of metabolic and inflammatory complications in RA. The recent discovery of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous inverse agonist/antagonist of the ghrelin receptor makes feasible the development of a more rational pharmacological approach. This work aimed to assess the serum LEAP2 levels, in a cohort of RA patients, in comparison with healthy individuals and determine its correlation with inflammatory parameters. LEAP2 levels were determined by a commercial ELISA kit, plasma C-reactive protein (CRP) levels were evaluated using immunoturbidimetry, and serum levels of inflammatory mediators, namely IL-6, IL-8, IL-1 beta, MIP1 alpha, MCP1, and LCN2, were measured by XMap multiplex assay. LEAP2 serum levels were significantly increased in RA patients (n = 101) compared with control subjects (n = 26). Furthermore, the LEAP2 levels significantly correlated with CRP and inflammatory cytokines, but not with BMI. These data reveal LEAP2 as a new potential RA biomarker and indicated the pharmacological control of LEAP2 levels as a novel approach for the treatment of diseases with alterations on the ghrelin levels, such as rheumatoid cachexia.