Cohen Danielle, Koopmans Marije, Kremer Hovinga Idske C L, Berger Stefan P, Roos van Groningen Marian, Steup-Beekman Gerda M, de Heer Emile, Bruijn Jan Anthonie, Bajema Ingeborg M
Leiden University Medical Center, Leiden, The Netherlands.
Arthritis Rheum. 2008 Aug;58(8):2460-9. doi: 10.1002/art.23662.
In patients with systemic lupus erythematosus (SLE) and lupus nephritis, the presence of antiphospholipid antibodies (aPL) is considered to be an indication of increased risk of thrombotic microangiopathy, a serious complication of SLE. Previous studies have demonstrated a critical role for activation of the classical pathway of complement that leads to thrombotic injury in the presence of aPL. This study was undertaken to investigate whether C4d deposition in lupus nephritis is related to circulating aPL and the presence of renal microthrombi.
Deposition patterns of C4d in 44 renal biopsy samples obtained from 38 patients with biopsy-proven lupus nephritis were determined by staining with a polyclonal anti-C4d antibody. A phosphotungstic acid-hematoxylin stain was used to identify fibrin microthrombi. Clinical data (serum creatinine levels and presence or absence of aPL) were obtained and correlated with findings in the renal biopsy specimens. Patients were categorized as having aPL (n = 20) or not having aPL (n = 18).
A strong relationship between the intensity of glomerular C4d staining and the presence of microthrombi was found (P < 0.002). Intense glomerular C4d deposition was present in 7 of 8 biopsy samples showing renal microthrombi. Neither C4d deposition nor the presence of microthrombi was correlated with aPL status.
Our findings suggest that activation of the classical pathway of complement plays a pathogenic role in the development of renal tissue injury leading to thrombosis, irrespective of the type of circulating antibodies present. Immunodetection of glomerular C4d deposition in renal biopsy samples could be a convenient method of identifying patients at risk of thrombotic microangiopathy.
在系统性红斑狼疮（SLE）和狼疮性肾炎患者中，抗磷脂抗体（aPL）的存在被认为是血栓性微血管病风险增加的指标，血栓性微血管病是SLE的一种严重并发症。既往研究已证明，在aPL存在的情况下，补体经典途径的激活在导致血栓形成损伤中起关键作用。本研究旨在探讨狼疮性肾炎中C4d沉积是否与循环中的aPL及肾微血栓的存在有关。
用多克隆抗C4d抗体染色，确定从38例经活检证实为狼疮性肾炎的患者获取的44份肾活检样本中C4d的沉积模式。采用磷钨酸苏木精染色鉴定纤维蛋白微血栓。获取临床数据（血清肌酐水平及aPL的有无），并将其与肾活检标本的结果进行关联。患者被分为有aPL组（n = 20）和无aPL组（n = 18）。
发现肾小球C4d染色强度与微血栓的存在之间存在密切关系（P < 0.002）。在8份显示肾微血栓的活检样本中，有7份存在强烈的肾小球C4d沉积。C4d沉积及微血栓的存在均与aPL状态无关。
我们的研究结果表明，无论存在何种循环抗体，补体经典途径的激活在导致血栓形成的肾组织损伤发展中起致病作用。肾活检样本中肾小球C4d沉积的免疫检测可能是识别有血栓性微血管病风险患者的一种便捷方法。
