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Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation which are reversed by inflammation control
Rheumatology ( IF 5.5 ) Pub Date : 2022-08-10 , DOI: 10.1093/rheumatology/keac454
Rachel Audo 1, 2 , Pauline Sanchez 1 , Benjamin Rivière 3 , Julie Mielle 4 , Jian Tan 4 , Cédric Lukas 1 , Laurence Macia 4 , Jacques Morel 1, 2 , Claire Immediato Daien 1, 2
Affiliation  

Objective to assess how rheumatoid arthritis (RA) and Disease Modifying Anti Rheumatic Drugs (DMARDs) affect gut permeability. Methods to explore colonic mucosa integrity, tight junction proteins ZO-1, occludin and claudin 2 were quantified by immunohistochemistry on colonic biopsies in 20 RA patients and 20 age- and sex-matched controls. Staining intensity was assessed by two blinded independent readers. To explore intestinal permeability, serum concentrations of LPS-binding protein (LBP), sCD14 and zonulin-related proteins (ZRP) were evaluated by ELISA in another cohort of 59 RA: 21 patients naive of DMARDs (17 before and after introduction of a conventional synthetic (cs) DMARDs), 38 patients with severe RA (before and after introduction of a biological (b) DMARDs), and 33 healthy controls. Results Z0-1 protein was less expressed in colon of RA patients than controls (mean score ± SEM of 1.6 ± 0.56 vs 2.0 ± 0.43; p= 0.01), while no significant difference was detected for occludin and claudin-2. RA patients had higher serum LBP and sCD14 concentrations than controls. LBP and sCD14 levels were significantly correlated with DAS28 (r = 0.61, p= 0.005 and r = 0.57, p= 0.01, respectively) while ZRP did not. bDMARD responders had significantly reduced LBP and sCD14 concentrations unlike bDMARDs non-responders and patients treated with csDMARDs. Conclusion RA patients have altered colonic tight junction proteins and increased serum biomarkers of intestinal permeability. There was a correlation between serological markers of intestinal permeability and disease activity as well as bDMARD response. These results suggest a link between impaired gut integrity and systemic inflammation in RA.

中文翻译:

类风湿性关节炎与增加的肠道通透性和细菌易位有关,而炎症控制可以逆转这种情况

目的评估类风湿性关节炎 (RA) 和改善疾病的抗风湿药物 (DMARDs) 如何影响肠道通透性。探索结肠粘膜完整性、紧密连接蛋白 ZO-1、occludin 和 claudin 2 的方法通过对 20 名 RA 患者和 20 名年龄和性别匹配的对照的结肠活检进行免疫组织化学定量。染色强度由两名不知情的独立读者评估。为了探索肠道通透性,通过 ELISA 在另一组 59 名 RA 中评估 LPS 结合蛋白 (LBP)、sCD14 和连蛋白相关蛋白 (ZRP) 的血清浓度:21 名未接受 DMARD 的患者(17 名在引入常规合成 (cs) DMARDs)、38 名严重 RA 患者(在引入生物 (b) DMARDs 之前和之后)和 33 名健康对照。结果 Z0-1 蛋白在 RA 患者结肠中的表达低于对照组(平均评分 ± SEM 为 1.6 ± 0.56 vs 2.0 ± 0.43;p = 0.01),而 occludin 和 claudin-2 未检测到显着差异。RA 患者的血清 LBP 和 sCD14 浓度高于对照组。LBP 和 sCD14 水平与 DAS28 显着相关(分别为 r = 0.61,p = 0.005 和 r = 0.57,p = 0.01),而 ZRP 则没有。与 bDMARD 无反应者和接受 csDMARD 治疗的患者不同,bDMARD 反应者的 LBP 和 sCD14 浓度显着降低。结论 RA 患者结肠紧密连接蛋白发生改变,肠道通透性血清生物标志物增加。肠道通透性的血清学标志物与疾病活动以及 bDMARD 反应之间存在相关性。
更新日期:2022-08-10
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