补体蛋白L-纤维胶凝蛋白和M-纤维胶凝蛋白在强直性脊柱炎患者中升高，在肿瘤坏死因子抑制剂治疗后降低。
Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment.
作者信息
Mistegaard Clara Elbæk, Troldborg Anne, Hansen Annette, Thiel Steffen, Jurik Anne Grethe, Kiil Rosa M, Christiansen Alice A, Schiøttz-Christensen Berit, Hendricks Oliver, Pedersen Susanne Juhl, Sørensen Inge Juul, Østergaard Mikkel, Loft Anne Gitte
机构信息
C.E. Mistegaard, MD, Department of Rheumatology, Aarhus University Hospital, Aarhus, Department of Clinical Medicine, Aarhus University, Aarhus, Institute of Regional Health Research, University of Southern Denmark, Odense, and Department of Biomedicine, Aarhus University, Aarhus.
A. Troldborg, MD, PhD, Department of Rheumatology, Aarhus University Hospital, Aarhus, Department of Clinical Medicine, Aarhus University, Aarhus, and Department of Biomedicine, Aarhus University, Aarhus.
出版信息
J Rheumatol. 2023 Sep 15. doi: 10.3899/jrheum.2023-0164.
OBJECTIVE
We have previously reported elevated levels of the complement lectin pathway proteins L-ficolin and H-ficolin in patients with axial spondyloarthritis (axSpA) compared with healthy controls. The aim of the present study was to investigate these biomarkers in a cross-sectional cohort of patients suffering from low back pain (LBP). Further, we aimed to investigate changes in lectin pathway protein levels after initiation of adalimumab (ADA; a tumor necrosis factor inhibitor) in a longitudinal cohort of patients with axSpA.
METHODS
Lectin pathway protein levels (mannan-binding lectin [MBL], collectin liver 1, H-ficolin, L-ficolin, M-ficolin, MBL-associated serine protease [MASP]-1, MASP-2, MASP-3, MBL-associated protein 19 [MAp19], and MAp44) in EDTA plasma were determined in 2 well-characterized cohorts: (1) a clinical cross-sectional cohort of patients with LBP, including patients with axSpA (n = 23), patients with unspecific LBP (uLBP) with ≥ 1 SpA features (n = 55), and patients with uLBP without SpA features or magnetic resonance imaging findings suggestive of axSpA (n = 64); and (2) a randomized double-blinded, placebo-controlled trial cohort of patients with axSpA (n = 49) initiating ADA therapy. Lectin pathway protein levels were determined using immunoassays.
RESULTS
Plasma levels of L-ficolin and M-ficolin were significantly increased in the cross-sectional cohort of newly diagnosed patients with axSpA compared with clinically relevant controls with uLBP (all < 0.05). Both L-ficolin and M-ficolin decreased significantly after ADA therapy ( < 0.05).
CONCLUSION
L-ficolin and M-ficolin levels are elevated in newly diagnosed patients with axSpA compared with clinically relevant controls. Both L-ficolin and M-ficolin levels decrease significantly after initiating ADA therapy. These findings provide new insights into the inflammatory processes in axSpA and support the involvement of complement in axSpA pathogenesis.
目的
我们之前报道过，与健康对照相比，强直性脊柱炎（axSpA）患者体内补体凝集素途径蛋白L-纤维胶凝蛋白和H-纤维胶凝蛋白水平升高。本研究的目的是在一个下腰痛（LBP）患者的横断面队列中研究这些生物标志物。此外，我们旨在研究axSpA患者纵向队列中使用阿达木单抗（ADA；一种肿瘤坏死因子抑制剂）治疗开始后凝集素途径蛋白水平的变化。
方法
在2个特征明确的队列中测定乙二胺四乙酸（EDTA）血浆中的凝集素途径蛋白水平（甘露聚糖结合凝集素[MBL]、肝脏凝集素1、H-纤维胶凝蛋白、L-纤维胶凝蛋白、M-纤维胶凝蛋白、MBL相关丝氨酸蛋白酶[MASP]-1、MASP-2、MASP-3、MBL相关蛋白19[MAp19]和MAp44）：（1）一个LBP患者的临床横断面队列，包括axSpA患者（n = 23）、具有≥1个SpA特征的非特异性LBP（uLBP）患者（n = 55）以及无SpA特征或磁共振成像结果提示axSpA的uLBP患者（n = 64）；（2）一个开始ADA治疗的axSpA患者随机双盲、安慰剂对照试验队列（n = 49）。使用免疫测定法测定凝集素途径蛋白水平。
结果
与具有uLBP的临床相关对照相比，新诊断的axSpA患者横断面队列中L-纤维胶凝蛋白和M-纤维胶凝蛋白的血浆水平显著升高（均P < 0.05）。ADA治疗后，L-纤维胶凝蛋白和M-纤维胶凝蛋白均显著降低（P < 0.05）。
结论
与临床相关对照相比，新诊断的axSpA患者中L-纤维胶凝蛋白和M-纤维胶凝蛋白水平升高。开始ADA治疗后，L-纤维胶凝蛋白和M-纤维胶凝蛋白水平均显著降低。这些发现为axSpA的炎症过程提供了新的见解，并支持补体参与axSpA发病机制。
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