系统性红斑狼疮患者补体激活的凝集素途径。
The Lectin Pathway of Complement Activation in Patients with Systemic Lupus Erythematosus.
机构信息
From the Department of Rheumatology, Aarhus University Hospital; Institute of Clinical Medicine, and Department of Biomedicine, Aarhus University, Aarhus; Department of Clinical Immunology, Aalborg University Hospital, Aalborg; Department of Cancer and Inflammation Research, University of Southern Denmark; Department of Rheumatology, Odense University Hospital, Odense, Denmark; Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
A. Troldborg, MD, PhD, Department of Rheumatology, Aarhus University Hospital, and Institute of Clinical Medicine, Aarhus University; S. Thiel, PhD, Professor, Department of Biomedicine, Aarhus University; M. Trendelenburg, PhD, Professor, Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; J. Friebus-Kardash, MD, Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; J. Nehring, MD, Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; R. Steffensen, PhD, Department of Clinical Immunology, Aalborg University Hospital; S.W. Hansen, PhD, Associate Professor, Department of Cancer and Inflammation Research, University of Southern Denmark; M.J. Laska, PhD, Associate Professor, Institute of Clinical Medicine, Aarhus University, and Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; B. Deleuran, PhD, Professor, Department of Rheumatology, Aarhus University Hospital, and Department of Biomedicine, Aarhus University; J.C. Jensenius, PhD, Professor, Department of Biomedicine, Aarhus University; A. Voss, MD, PhD, Department of Rheumatology, Odense University Hospital; K. Stengaard-Pedersen, PhD, Professor, Department of Rheumatology, Aarhus University Hospital, and Institute of Clinical Medicine, Aarhus University.
出版信息
J Rheumatol. 2018 Aug;45(8):1136-1144. doi: 10.3899/jrheum.171033. Epub 2018 Jun 15.
OBJECTIVE
The pathogenesis of systemic lupus erythematosus (SLE) involves complement activation. Activation of complement through the classical pathway (CP) is well established. However, complement activation through pattern recognition not only happens through the CP, but also through the lectin pathway (LP). We investigated the hypothesis that the LP is activated in SLE and involved in the pathogenesis of the disease.
METHODS
Using immunoassays developed in-house, we measured concentrations of LP proteins in a cohort of 372 patients with SLE and 170 controls. We estimated complement activation measuring total C3, and investigated whether LP protein concentrations were associated with complement activation and disease activity. Protein changes and disease activity over time were assessed in a cohort of 52 patients with SLE followed with repeated samples over a 5-year period.
RESULTS
Concentrations of LP proteins in SLE were altered compared with controls. The differences observed in LP proteins associated with complement activation were reflected by a decrease in total C3. The pattern recognition molecules (M-ficolin, CL-L1, and CL-K1), the serine protease (MASP-3), and the associated protein (MAp19) displayed a negative correlation with disease activity. Changes in MASP-2 concentrations over time correlated significantly with increased disease activity. Association between active proteinuria and serum concentration was observed for MASP-3 and MAp19.
CONCLUSION
In patients with SLE, we measured specific changes in LP proteins that are associated with complement activation and disease activity, indicating that the LP is activated in patients with SLE. These novel findings substantiate the involvement of the LP in SLE.
目的
系统性红斑狼疮（SLE）的发病机制涉及补体激活。经典途径（CP）激活补体已得到充分证实。然而，模式识别途径（LP）不仅通过 CP 发生，而且通过 LP 发生补体激活。我们假设 LP 在 SLE 中被激活，并参与疾病的发病机制。
方法
使用内部开发的免疫测定法，我们测量了 372 例 SLE 患者和 170 例对照者的 LP 蛋白浓度。我们通过测量总 C3 来估计补体激活情况，并研究 LP 蛋白浓度是否与补体激活和疾病活动相关。我们评估了一组 52 例 SLE 患者的蛋白变化和疾病活动随时间的变化，这些患者在 5 年内进行了重复样本检测。
结果
与对照组相比，SLE 患者的 LP 蛋白浓度发生了改变。与补体激活相关的 LP 蛋白差异反映在总 C3 的减少上。模式识别分子（M-ficolin、CL-L1 和 CL-K1）、丝氨酸蛋白酶（MASP-3）和相关蛋白（MAp19）与疾病活动呈负相关。MASP-2 浓度随时间的变化与疾病活动的增加显著相关。MASP-3 和 MAp19 的血清浓度与蛋白尿的变化与疾病活动呈正相关。
结论
在 SLE 患者中，我们测量了与补体激活和疾病活动相关的 LP 蛋白的特定变化，表明 LP 在 SLE 患者中被激活。这些新发现证实了 LP 在 SLE 中的参与。
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