From the Division of Rheumatology, Department of Medicine, Department of Molecular Medicine and Surgery, Clinical Chemistry, and Renal Medicine, Karolinska Institutet; Rheumatology, Karolinska University Hospital; CLINTEC Karolinska University Hospital, Renal Medicine, Karolinska Institutet, Stockholm; Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Pediatrics, Medical Faculty, University of Niš, Niš, Serbia.
A. Antovic, MD, PhD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital; F. Mobarrez, PhD, Department of Medical Sciences, Uppsala University; M. Manojlovic, MD, Department of Pediatrics, Medical Faculty, University of Niš; N. Soutari, BMS, MS, Department of Molecular Medicine and Surgery, Clinical Chemistry, Karolinska Institutet; V. De Porta Baggemar, MD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital; A. Nordin, MD, PhD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital; A. Bruchfeld, MD, PhD, Renal Medicine, CLINTEC Karolinska University Hospital and Karolinska Institutet; J. Vojinovic, MD, PhD, Department of Pediatrics, Medical Faculty, University of Niš; I. Gunnarsson, MD, PhD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital.
J Rheumatol. 2020 May 1;47(5):714-721. doi: 10.3899/jrheum.181347. Epub 2019 Aug 1.
To investigate expression of terminal complement components C3a and C5a on circulating myeloperoxidase (MPO)-positive microparticles (MPO+MP) in relation to disease activity and renal involvement in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
Forty-six clinically well-characterized patients with AAV and 23 age- and sex-matched healthy controls were included. The concentration of MPO+MP expressing C3a and C5a was analyzed from citrate plasma by flow cytometry. Serum levels of C3a and C5a were determined using commercial ELISA. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS). Among patients, 23 had active disease with BVAS ≥ 2 and 14 patients had active renal flares.
AAV patients had significantly increased expression of C3a and C5a on MPO+MP compared to controls (both p < 0.0001). When the group of patients with active AAV was divided according to the presence of renal activity, the concentration of MPO+MP expressing C3a and C5a was significantly higher in patients with renal involvement compared to patients with nonrenal disease and controls (p < 0.05 and p < 0.01, respectively). The serum levels of C3a were significantly decreased (p < 0.01) in the renal subgroup, while there were no changes in serum levels of C5a comparing the renal and nonrenal groups. There was significant correlation between the disease activity measured by BVAS and the levels of C3a and C5a expressed on MPO+MP.
Determination of C3a and C5a on MPO+MP might be considered as a novel biomarker of renal involvement in patients with AAV and may be of importance in the pathogenetic process.
研究补体末端成分 C3a 和 C5a 在循环髓过氧化物酶（MPO）阳性微颗粒（MPO+MP）上的表达与抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）患者的疾病活动和肾脏受累的关系。
纳入 46 例临床特征明确的 AAV 患者和 23 名年龄和性别匹配的健康对照者。通过流式细胞术分析柠檬酸盐血浆中表达 C3a 和 C5a 的 MPO+MP 的浓度。使用商业 ELISA 测定血清中 C3a 和 C5a 的水平。采用伯明翰血管炎活动评分（BVAS）评估血管炎疾病活动度。在患者中，23 例疾病活动度≥2 的患者为活动期，14 例患者出现活动期肾脏炎。
与对照组相比，AAV 患者 MPO+MP 上 C3a 和 C5a 的表达明显增加（均 p<0.0001）。当根据肾脏活性将活动期 AAV 患者分组时，与非肾脏疾病患者和对照组相比，有肾脏受累的患者 MPO+MP 上表达的 C3a 和 C5a 的浓度明显更高（分别为 p<0.05 和 p<0.01）。肾亚组中血清 C3a 水平显著降低（p<0.01），而比较肾和非肾组之间，血清 C5a 水平无变化。BVAS 测量的疾病活动度与 MPO+MP 上表达的 C3a 和 C5a 水平之间存在显著相关性。
MPO+MP 上 C3a 和 C5a 的测定可被视为 AAV 患者肾脏受累的新型生物标志物，可能在发病机制中具有重要意义。
