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趋化素和色素上皮衍生因子是类风湿关节炎中与炎症相关的疾病活动和肥胖生物标志物。

Chemerin and PEDF Are Metaflammation-Related Biomarkers of Disease Activity and Obesity in Rheumatoid Arthritis.

作者信息

Tolusso Barbara, Gigante Maria Rita, Alivernini Stefano, Petricca Luca, Fedele Anna Laura, Di Mario Clara, Aquilanti Barbara, Magurano Maria Rosaria, Ferraccioli Gianfranco, Gremese Elisa

机构信息

Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy.

Service of Dietary and Human Nutrition, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy.

出版信息

Front Med (Lausanne). 2018 Aug 3;5:207. doi: 10.3389/fmed.2018.00207. eCollection 2018.

Abstract

Obesity is a risk factor for Rheumatoid Arthritis (RA) being associated to low grade inflammation. This study aimed to determine whether PEDF and Chemerin are biomarkers of inflammation related to fat accumulation in RA and to investigate whether weight loss associates with clinical disease improvement through the modification of fat-related biomarkers in overweight/obese RA with low-moderate disease. Two-hundred and thirty RA patients were enrolled, of whom 176 at disease onset treated according to a treat-to-target strategy (T2T) and 54 overweight/obese RA in stable therapy and low-moderate disease activity. Gene expression of adipokines, interleukin-6 and their receptors were examined in adipose tissue from obese RA. Obese RA with low-moderate disease activity underwent low-calories diet aiming to Body Mass Index (BMI) reduction >5%, maintaining RA therapy unchanged. Chemerin, PEDF and Interleukin-6 plasma values were assessed by ELISA and disease activity was evaluated. At RA onset, PEDF and Chemerin plasma values correlated with BMI ( < 0.001) but only Chemerin plasma values correlated with disease activity ( < 0.001). After adopting a T2T strategy, Chemerin arose as an independent factor associated with remission in early RA [OR(95%CIs):0.49(0.25-0.97)]. Moreover, after low-calories diet, RA with low-moderate disease activity reaching BMI reduction ≥5% (62.6%) at 6 months had significant decrease of PEDF ( < 0.05) and Chemerin ( < 0.05) plasma values, in parallel with the improvement in disease activity. PEDF and Chemerin arose as biomarkers of obesity and metaflammation respectively, providing a link between chronic inflammation and excess of body weight in RA. Therefore, BMI reduction of at least 5% in obese RA allowed better disease control without modifying RA treatment.

摘要

肥胖是类风湿关节炎(RA)的一个风险因素,与低度炎症相关。本研究旨在确定色素上皮衍生因子(PEDF)和趋化素是否为与RA中脂肪堆积相关的炎症生物标志物,并调查体重减轻是否通过改变超重/肥胖且疾病程度为低中度的RA患者中与脂肪相关的生物标志物而与临床疾病改善相关。招募了230例RA患者,其中176例在疾病发作时按照达标治疗策略(T2T)进行治疗,54例超重/肥胖的RA患者处于稳定治疗且疾病活动程度为低中度。检测了肥胖RA患者脂肪组织中脂肪因子、白细胞介素-6及其受体的基因表达。疾病活动程度为低中度的肥胖RA患者接受低热量饮食,目标是体重指数(BMI)降低>5%,同时维持RA治疗不变。通过酶联免疫吸附测定(ELISA)评估趋化素、PEDF和白细胞介素-6的血浆值,并评估疾病活动度。在RA发作时,PEDF和趋化素的血浆值与BMI相关(<0.001),但只有趋化素的血浆值与疾病活动度相关(<0.001)。采用T2T策略后,趋化素成为与早期RA缓解相关的独立因素[比值比(95%可信区间):0.49(0.25-0.97)]。此外,低热量饮食后,疾病活动程度为低中度且在6个月时BMI降低≥5%的RA患者(62.6%),其PEDF(<0.05)和趋化素(<0.05)的血浆值显著降低,同时疾病活动度有所改善。PEDF和趋化素分别成为肥胖和代谢性炎症的生物标志物,在RA中建立了慢性炎症与体重超重之间的联系。因此,肥胖RA患者BMI降低至少5%可在不改变RA治疗的情况下实现更好的疾病控制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c6/6085446/4369db38d0b4/fmed-05-00207-g0001.jpg

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