Arias-de la Rosa Iván, Escudero-Contreras Alejandro, Ruiz-Ponce Miriam, Cuesta-López Laura, Román-Rodríguez Cristóbal, Pérez-Sánchez Carlos, Ruiz-Limón Patricia, Ruiz Rocío Guzman-, Leiva-Cepas Fernando, Alcaide Juan, Segui Pedro, Plasencia Chamaida, Martinez-Feito Ana, Font Pilar, Ábalos María C, Ortega Rafaela, Malagón María M, Tinahones Francisco J, Collantes-Estévez Eduardo, López-Pedrera Chary, Barbarroja Nuria
GENYO (Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada, Granada, Spain.
Rheumatology Service/Department of Medical and Surgical Sciences, Maimonides Institute for Biomedicine Research of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain.
iScience. 2022 Aug 6;25(9):104893. doi: 10.1016/j.isci.2022.104893. eCollection 2022 Sep 16.
We aimed to evaluate the association between adipose tissue (AT) dysfunction, autoimmunity, and disease activity in rheumatoid arthritis (RA). A cross-sectional study including 150 RA patients and 50 healthy donors and longitudinal study with 122 RA patients treated with anti-tumor necrosis factor (TNF)-α, anti-interleukin 6 receptor (IL6R) or anti-CD20 therapies for 6 months were carried out. experiments with human AT and adipocyte and macrophage cell lines were performed. A collagen-induced arthritis mouse model was developed. The insulin resistance and the altered adipocytokine profile were associated with disease activity, the presence of anti-citrullinated proteins anti-bodies (ACPAs), and worse response to therapy in RA. AT in the context of arthritis is characterized by an inflammatory state alongside the infiltration of macrophages and B/plasmatic cells, where ACPAs can have a direct impact, inducing inflammation and insulin resistance in macrophages and promoting a defective adipocyte differentiation, partially restored by biologicals.
我们旨在评估类风湿关节炎（RA）中脂肪组织（AT）功能障碍、自身免疫与疾病活动之间的关联。开展了一项横断面研究，纳入150例RA患者和50例健康供者，并对122例接受抗肿瘤坏死因子（TNF）-α、抗白细胞介素6受体（IL6R）或抗CD20治疗6个月的RA患者进行了纵向研究。进行了用人AT以及脂肪细胞和巨噬细胞系的实验。建立了胶原诱导性关节炎小鼠模型。胰岛素抵抗和脂肪细胞因子谱改变与疾病活动、抗瓜氨酸化蛋白抗体（ACPA）的存在以及RA患者对治疗的较差反应相关。关节炎背景下的AT以炎症状态为特征，同时伴有巨噬细胞和B/浆细胞浸润，ACPA可在其中产生直接影响，诱导巨噬细胞炎症和胰岛素抵抗，并促进脂肪细胞分化缺陷，生物制剂可部分恢复这种缺陷。
