Rademacher Judith, Torgutalp Murat, Hempel Christine Maria, Proft Fabian, Haibel Hildrun, Protopopov Mikhail, Spiller Laura, Poddubnyy Denis, Rios Rodriguez Valeria
Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
RMD Open. 2024 Dec 31;10(4):e004752. doi: 10.1136/rmdopen-2024-004752.
The objective of this study is to investigate lipopolysaccharid-binding protein (LBP), zonulin and calprotectin as markers of bacterial translocation, disturbed gut barrier and intestinal inflammation in patients with radiographic axial spondyloarthritis (r-axSpA) during tumour necrosis factor inhibitor (TNFi) therapy and to analyze the association between disease activity, response to treatment and biomarker levels.
Patients with active r-axSpA of the German Spondyloarthritis Inception Cohort starting TNFi were compared with controls with chronic back pain. Serum levels of LBP, zonulin and calprotectin were measured at baseline and after 1 year of TNFi therapy. We analysed the longitudinal association between biomarkers and disease activity, and the relationship between biomarkers and treatment response with regression analysis.
121 patients with r-axSpA were compared with 63 controls. At baseline, patients with r-axSpA had higher levels of LBP and calprotectin than controls, which decreased significantly during TNFi treatment. LBP showed a positive association in longitudinal analyses with Axial Spondyloarthritis Disease Activity Score (ASDAS) (ß=0.08, 95% CI 0.06 to 0.10), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (ß=0.08, 95% CI 0.04 to 0.12) and C reactive protein (CRP) (ß=1.69, 95% CI 1.04 to 2.34). Calprotectin was associated with ASDAS (ß=0.04, 95% CI 0.01 to 0.07) and CRP (ß=0.82, 95% CI 0.27 to 1.37). Furthermore, LBP and calprotectin levels at baseline showed an association with a subsequent change in BASDAI. Baseline zonulin levels were not significantly associated with disease activity or treatment response.
Serum levels of LBP and calprotectin are associated with disease activity in patients with r-axSpA and decrease with TNFi response. In contrast, serum zonulin levels showed no association with disease activity or treatment response, arguing against a strict correlation between intestinal permeability and disease activity in axSpA.
本研究的目的是调查脂多糖结合蛋白（LBP）、闭合蛋白和钙卫蛋白作为影像学轴向脊柱关节炎（r-axSpA）患者在肿瘤坏死因子抑制剂（TNFi）治疗期间细菌易位、肠道屏障紊乱和肠道炎症的标志物，并分析疾病活动度、治疗反应与生物标志物水平之间的关联。
将德国脊柱关节炎起始队列中开始使用TNFi的活动性r-axSpA患者与慢性背痛患者进行比较。在基线和TNFi治疗1年后测量血清LBP、闭合蛋白和钙卫蛋白水平。我们通过回归分析分析了生物标志物与疾病活动度之间的纵向关联，以及生物标志物与治疗反应之间的关系。
121例r-axSpA患者与63例对照进行了比较。在基线时，r-axSpA患者的LBP和钙卫蛋白水平高于对照，在TNFi治疗期间显著下降。LBP在纵向分析中与轴向脊柱关节炎疾病活动评分（ASDAS）（β=0.08，95%CI 0.06至0.10）、巴斯强直性脊柱炎疾病活动指数（BASDAI）（β=0.08，95%CI 0.04至0.12）和C反应蛋白（CRP）（β=1.69，95%CI 1.04至2.34）呈正相关。钙卫蛋白与ASDAS（β=0.04，95%CI 0.01至0.07）和CRP（β=0.82，95%CI 0.27至1.37）相关。此外，基线时的LBP和钙卫蛋白水平与BASDAI的后续变化相关。基线闭合蛋白水平与疾病活动度或治疗反应无显著关联。
r-axSpA患者的血清LBP和钙卫蛋白水平与疾病活动度相关，并随TNFi反应而降低。相比之下，血清闭合蛋白水平与疾病活动度或治疗反应无关联, 这表明轴向脊柱关节炎中肠道通透性与疾病活动度之间不存在严格的相关性。
