SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain.
Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela and Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain and CIBER Fisiopatología, de la Obesidad y Nutrición (CIBERobn), Spain.
Nutrients. 2020 Apr 6;12(4):1006. doi: 10.3390/nu12041006.
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-1β, MIP1α, MCP1, and LCN2, were measured by XMap multiplex assay. LEAP2 serum levels were significantly increased in RA patients ( = 101) compared with control subjects ( = 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.
类风湿关节炎（RA）是一种使人衰弱的、慢性的、炎症性的、自身免疫性疾病，与恶病质有关。肠激素胃饥饿素的替代疗法已被指出是治疗 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）作为胃饥饿素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。本研究旨在评估 RA 患者队列中的血清 LEAP2 水平，与健康个体进行比较，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，通过 XMap 多重分析测定炎症介质 IL-6、IL-8、IL-1β、MIP1α、MCP1 和 LCN2 的血清水平。与对照组（ = 26）相比，RA 患者（ = 101）的血清 LEAP2 水平显著升高。此外，LEAP2 水平与 CRP 和炎症细胞因子显著相关，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，并表明控制 LEAP2 水平作为治疗胃饥饿素水平改变的疾病（如类风湿性恶病质）的新方法。
