Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
Scand J Rheumatol. 2020 Jul;49(4):301-311. doi: 10.1080/03009742.2019.1695927. Epub 2020 Apr 14.
The complement cascade, especially the alternative pathway of complement, has been shown in basic research to be associated with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). We aimed to elucidate relationships between serum complement components and clinical characteristics in AAV.
In a nationwide prospective cohort study (RemIT-JAV-RPGN), we measured the serum levels of C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, factor B, factor D, factor H, factor I, mannose-binding lectin, and properdin in 52 patients with microscopic polyangiitis (MPA) and 39 patients with granulomatosis with polyangiitis (GPA).
The properdin level of MPA and GPA was significantly lower than that of healthy donors. The properdin level was negatively correlated with the Birmingham Vasculitis Activity Score (BVAS) (ρ = -0.2148, p = 0.0409). The factor D level at 6 months was significantly positively correlated with the Vasculitis Damage Index (VDI) at 6, 12, and 24 months (ρ = 0.4207, 0.4132, and 0.3115, respectively). Patients with a higher ratio of C5a to C5 had higher neutrophil percentage and serum immunoglobulin G levels, and significantly lower creatinine levels. Cluster analysis divided the MPA and GPA patients into three subgroups. A principal component (PC) analysis aggregated 15 types of complements into alternative pathway-related PC 1 and complement classical pathway and common pathway-related PC 2.
The serum levels of properdin and factor D were correlated with the BVAS and the VDI in MPA and GPA, respectively. Our analyses suggested the pathological heterogeneity of MPA and GPA from the aspect of complement components.
补体级联反应，尤其是补体的替代途径，在基础研究中已被证明与抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）有关。我们旨在阐明 AAV 患者血清补体成分与临床特征之间的关系。
在一项全国性前瞻性队列研究（RemIT-JAV-RPGN）中，我们测量了 52 例显微镜下多血管炎（MPA）和 39 例肉芽肿性多血管炎（GPA）患者的血清 C1q、C2、C3、C3b/iC3b、C4、C4b、C5、C5a、C9、因子 B、因子 D、因子 H、因子 I、甘露聚糖结合凝集素和备解素水平。
MPA 和 GPA 的备解素水平明显低于健康供者。备解素水平与伯明翰血管炎活动评分（BVAS）呈负相关（ρ=-0.2148，p=0.0409）。6 个月时的因子 D 水平与 6、12 和 24 个月时的血管炎损伤指数（VDI）呈显著正相关（ρ=0.4207、0.4132 和 0.3115）。C5a 与 C5 比值较高的患者中性粒细胞百分比和血清 IgG 水平较高，而肌酐水平较低。聚类分析将 MPA 和 GPA 患者分为三组。主成分（PC）分析将 15 种补体聚集成替代途径相关的 PC1 和补体经典途径和共同途径相关的 PC2。
MPA 和 GPA 患者的血清备解素和因子 D 水平分别与 BVAS 和 VDI 相关。我们的分析从补体成分方面提示了 MPA 和 GPA 的病理异质性。
