Manzi S, Rairie J E, Carpenter A B, Kelly R H, Jagarlapudi S P, Sereika S M, Medsger T A, Ramsey-Goldman R
University of Pittsburgh School of Medicine, Pennsylvania, USA.
Arthritis Rheum. 1996 Jul;39(7):1178-88. doi: 10.1002/art.1780390716.
To determine if measurement of serum complement split products (C4d, Bb, C5b-9) is better than conventional C3 and C4 measurements in distinguishing patients with varying degrees of lupus disease activity, and to determine if the presence of C3d in urine is helpful in distinguishing lupus patients with from those without early lupus nephritis.
Lupus disease activity was prospectively determined at 3 consecutive visits an average of 4 months apart, using the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and physician global assessment (PGA). Blood samples were evaluated for the presence of C4d, Bb, and C5b-9 by quantitative microassay plate enzyme immunoassay at each patient visit. We characterized urinary excretion of C3 fragments (with attention to C3d) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western blotting.
Thirty-one SLE patients were enrolled in the study. The mean SLAM score and the mean SLEDAI score each correlated well with the PGA at all 3 visits. A SLAM score of 6 and a SLEDAI score of 4 had the best overall sensitivity and specificity for predicting moderate-to-severe disease activity by PGA (100% and 73%, respectively, for the SLAM and 86% and 94%, respectively, for the SLEDAI). Serum C4d and Bb were more sensitive indicators of current moderate-to-severe lupus disease activity at all 3 visits than were serum C5b-9, C3, and C4. C3 and C4 were more specific indicators of moderate-to-severe disease activity. Serum C4d and Bb were more sensitive at predicting moderate-to-severe disease activity at subsequent visits than were C5b-9, C3, and C4. Urine C3d was better than C3, plasma C4d, Bb, C5b-9 and anti-double-stranded DNA antibody in distinguishing patients with from those without acute lupus nephritis (P = 0.02).
C4d and Bb are sensitive indicators of moderate-to-severe lupus disease activity and may be most helpful in situations where conventional measurements are not, such as in lupus patients whose C3 and C4 levels remain normal despite evidence of clinical disease activity. It appears from this study that detection of urine C3d may be a simple way of measuring complement activation in the setting of lupus renal disease. The availability of instruments for clinical disease activity measurement such as the SLAM and the SLEDAI may enable more consistent definition of lupus disease activity and may thus provide a means for better examining the role of complement activation products in predicting lupus disease activity in larger patient populations.
确定检测血清补体裂解产物（C4d、Bb、C5b - 9）在区分不同程度狼疮疾病活动度的患者中是否优于传统的C3和C4检测，以及确定尿中C3d的存在是否有助于区分狼疮性肾炎患者和无早期狼疮性肾炎的患者。
前瞻性地在平均间隔4个月的连续3次就诊时，使用系统性狼疮活动度量表（SLAM）、系统性红斑狼疮疾病活动指数（SLEDAI）和医生整体评估（PGA）来确定狼疮疾病活动度。每次患者就诊时，通过定量微孔板酶免疫测定法评估血样中C4d、Bb和C5b - 9的存在情况。我们通过十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳和蛋白质印迹法对C3片段的尿排泄情况（关注C3d）进行了特征分析。
31例系统性红斑狼疮患者纳入本研究。在所有3次就诊时，平均SLAM评分和平均SLEDAI评分与PGA均具有良好的相关性。SLAM评分为6和SLEDAI评分为4对通过PGA预测中度至重度疾病活动度具有最佳的总体敏感性和特异性（SLAM分别为100%和73%，SLEDAI分别为86%和94%）。在所有3次就诊时，血清C4d和Bb作为当前中度至重度狼疮疾病活动度的指标比血清C5b - 9、C3和C4更敏感。C3和C4是中度至重度疾病活动度更具特异性的指标。血清C4d和Bb在预测后续就诊时的中度至重度疾病活动度方面比C5b - 9、C3和C更为敏感。尿C3d在区分急性狼疮性肾炎患者和无急性狼疮性肾炎患者方面优于C3、血浆C4d、Bb、C5b - 9和抗双链DNA抗体（P = 0.02）。
C4d和Bb是中度至重度狼疮疾病活动度的敏感指标，在传统检测不适用的情况下可能最有帮助，例如在尽管有临床疾病活动证据但C3和C4水平仍保持正常的狼疮患者中。从本研究看来，检测尿C3d可能是在狼疮性肾病情况下测量补体激活的一种简单方法。SLAM和SLEDAI等临床疾病活动度测量工具的可用性可能使狼疮疾病活动度的定义更加一致，从而可能为更好地研究补体激活产物在预测更大患者群体狼疮疾病活动度中的作用提供一种手段。
