Measurement of erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus
Measurement of erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus
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DOI：
10.1002/art.20561
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发表时间：
2004-11-01
影响因子：
--
通讯作者：
Ahearn, JM
中科院分区：
文献类型：
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作者：
Manzi, S;Navratil, JS;Ahearn, JM
Objective. C4衍生的活化片段是存在于正常红细胞表面上的唯一补体配体。这一观察结果的意义尚不清楚，红细胞结合C4（E-C4）在人类疾病中的作用尚未探讨。系统性红斑狼疮（SLE）的发病机制比任何其他人类疾病的特征在于通过表达补体受体I（CRI）的红细胞清除携带补体的免疫复合物的缺陷。本研究旨在探讨SLE患者红细胞E-C4和E-CRI表达的异常模式是否反映了这些功能缺陷。我们对100例SLE患者、133例其他疾病患者和84例健康对照者进行了横断面研究。采用间接免疫荧光法和流式细胞仪测定红细胞C4d和CR 1水平。SLE患者E-C4d水平高于其他疾病患者（P <0.001），E-CR 1水平低于健康对照组（P <0.001）。与健康对照组相比，该试验对SLE的敏感性为81%，特异性为91%，对SLE与其他疾病的敏感性为72%，特异性为79%，总体阴性预测值为92%。这是第一次报告人类疾病中E-C4d水平异常。我们发现异常高水平的E-C4d和低水平的E-CRI是SLE的特征，这两种分子的联合检测对SLE的诊断具有较高的敏感性和特异性。E-C4d/E-CR 1水平的测定可能是对当前SLE诊断测试和标准的有益补充。
Objective. C4-derived activation fragments are the only complement ligands present on the surfaces of normal erythrocytes. The significance of this observation is unknown, and the role of erythrocyte-bound C4 (E-C4) in human disease has not been explored. More than any other human disease, the pathogenesis of systemic lupus erythematosus (SLE) has been characterized by defects in clearance of complement-bearing immune complexes via erythrocytes expressing complement receptor I (CRI). This study was undertaken to determine whether these functional defects might be reflected by abnormal patterns of E-C4 and E-CRI expression on erythrocytes of patients with SLE.Methods. We conducted a cross-sectional study of 100 patients with SLE, 133 patients with other diseases, and 84 healthy controls. Erythrocytes were characterized by indirect immunofluorescence and by flow cytometry for determination of levels of C4d and CR1.Results. Patients with SLE had higher levels of E-C4d and lower levels of E-CR1 than did patients with other diseases (P less than or equal to 0.001) or healthy controls (P less than or equal to 0.001). The test was 81% sensitive and 91% specific for SLE versus healthy controls and 72% sensitive and 79% specific for SLE versus other diseases, and it had an overall negative predictive value of 92%.Conclusion. This is the first report of abnormal levels of E-C4d in human disease. We found that abnormally high levels of E-C4d and low levels of E-CRI are characteristic of SLE, and combined measurement of the 2 molecules has high diagnostic sensitivity and specificity for lupus. Determination of E-C4d/E-CR1 levels may be a useful addition to current tests and criteria for SLE diagnosis.