Porchas-Quijada Mildren, Reyes-Castillo Zyanya, Muñoz-Valle José Francisco, Durán-Barragán Sergio, Aguilera-Cervantes Virginia, López-Espinoza Antonio, Vázquez-Del Mercado Mónica, Navarro-Meza Mónica, López-Uriarte Patricia
Instituto de Investigaciones en Comportamiento Alimentario y Nutrición, Centro Universitario del Sur, Universidad de Guadalajara, Ciudad Guzmán, Mexico.
Instituto de Investigaciones en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico.
Front Endocrinol (Lausanne). 2019 Apr 18;10:252. doi: 10.3389/fendo.2019.00252. eCollection 2019.
Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with increased risk of cardiovascular disease and metabolic alterations. The mechanisms underlying these alterations remain unclear. Ghrelin is a gastrointestinal hormone with potent effects on food intake, body weight, metabolism, and immune response. Recent studies reported the presence of anti-ghrelin autoantibodies in healthy subjects and the levels and affinity of these autoantibodies were altered in anorectic and obese individuals. In this cross-sectional study we analyzed anti-ghrelin autoantibodies in RA patients and evaluated its relationship with clinical, body-composition and metabolic parameters. Clinical measurements of RA patients included the disease activity score-28 (DAS-28), inflammatory biomarkers, autoantibodies (RF and anti-CCP), body composition, glucose and lipid profile. Serum ghrelin levels were measured by enzyme-linked immunosorbent assay (ELISA). Free and total anti-ghrelin autoantibodies quantification (IgG and IgA isotypes) was performed by in-house ELISA. RA patients had lower IgG anti-ghrelin autoantibodies levels and higher immune complexes percentage (IgG+ghrelin) compared to the control group, while the IgA anti-ghrelin autoantibodies showed no significant differences. In the bivariate analysis, the percentage of IgG anti-ghrelin immune complexes positively correlated with BMI and ghrelin whereas in the multivariate regression model, the variables associated were DAS-28, body weight, visceral fat, LDL-C and TG ( = 0.72). The percentage of IgA anti-ghrelin immune complexes positively correlated with RF and anti-CCP and the multivariate regression model showed an association with RF and body fat percentage ( = 0.22). Our study shows an increased percentage of IgG anti-ghrelin immune complexes in RA patients despite ghrelin levels were similar in both groups, suggesting an increase in the affinity of these autoantibodies toward ghrelin. The associations found in the multiple regression analysis for anti-ghrelin immune complexes support the previously reported functions of these natural autoantibodies as carriers and modulators of the stability and physiological effect of the hormone. However, in RA both the disease activity and the RF appear to influence the formation of these anti-ghrelin immune complexes.
类风湿关节炎（RA）是一种全身性自身免疫性疾病，与心血管疾病风险增加和代谢改变有关。这些改变背后的机制尚不清楚。胃饥饿素是一种胃肠激素，对食物摄入、体重、代谢和免疫反应有显著影响。最近的研究报道健康受试者体内存在抗胃饥饿素自身抗体，且这些自身抗体的水平和亲和力在食欲缺乏和肥胖个体中发生了改变。在这项横断面研究中，我们分析了RA患者体内的抗胃饥饿素自身抗体，并评估了其与临床、身体成分和代谢参数的关系。RA患者的临床测量指标包括疾病活动评分-28（DAS-28）、炎症生物标志物、自身抗体（RF和抗环瓜氨酸肽抗体）、身体成分、血糖和血脂谱。血清胃饥饿素水平通过酶联免疫吸附测定（ELISA）进行测量。游离和总抗胃饥饿素自身抗体定量（IgG和IgA亚型）通过内部ELISA进行。与对照组相比，RA患者的IgG抗胃饥饿素自身抗体水平较低，免疫复合物百分比（IgG+胃饥饿素）较高，而IgA抗胃饥饿素自身抗体无显著差异。在双变量分析中，IgG抗胃饥饿素免疫复合物百分比与BMI和胃饥饿素呈正相关，而在多变量回归模型中，相关变量为DAS-28、体重、内脏脂肪、低密度脂蛋白胆固醇和甘油三酯（R² = 0.72）。IgA抗胃饥饿素免疫复合物百分比与RF和抗环瓜氨酸肽抗体呈正相关，多变量回归模型显示与RF和体脂百分比有关（R² = 0.22）。我们的研究表明，尽管两组胃饥饿素水平相似，但RA患者中IgG抗胃饥饿素免疫复合物百分比增加，表明这些自身抗体对胃饥饿素的亲和力增加。抗胃饥饿素免疫复合物在多元回归分析中发现的关联支持了先前报道的这些天然自身抗体作为激素稳定性和生理效应的载体和调节剂的功能。然而，在RA中，疾病活动度和RF似乎都影响这些抗胃饥饿素免疫复合物的形成。
