Sensitivity and specificity of plasma and urine complement split products as indicators of lupus disease activity

Sensitivity and specificity of plasma and urine complement split products as indicators of lupus disease activity
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DOI:
10.1002/art.1780390716
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发表时间:
1996-07-01
影响因子:
--
通讯作者:
RamseyGoldman, R
RamseyGoldman, R
中科院分区:
其他
文献类型:
--
作者:
Manzi, S;Rairie, JE;RamseyGoldman, R

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Objective.为了确定血清补体裂解产物(C4d、Bb、C5 b-9)的测量是否优于传统的C3和C4测量以区分不同程度的狼疮疾病活动性的患者,并且确定尿中C3 d的存在是否有助于区分早期狼疮肾炎的狼疮患者和没有狼疮肾炎的狼疮患者。狼疮疾病活动性是在3次连续访视时前瞻性确定的,平均间隔4个月,使用系统性狼疮活动性测量(SLAM)、系统性红斑狼疮疾病活动性指数(SLEDAI)和医生总体评估(PGA)。在每次患者访视时通过定量微量平板酶免疫测定法评估血液样品中C4d、Bb和C5 b-9的存在,通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳结合蛋白质印迹法表征C3片段(注意C3 d)的尿排泄。SLAM评分和SLEDAI评分均与PGA评分相关,SLAM评分为6分和SLEDAI评分为4分时,PGA评分预测中重度疾病活动度的敏感性和特异性最高(SLAM分别为100%和73%,SLEDAI分别为86%和94%),在所有3次访视中,血清C4d和Bb比血清C5 b-9、C3和C4更敏感,是当前中重度狼疮疾病活动的指标。C3和C4是中重度疾病活动度的更特异性指标,血清C4d和Bb在预测后续访视时的中重度疾病活动度方面比C5 b-9、C3和C4更敏感。尿C3 d在区分急性狼疮性肾炎与非急性狼疮性肾炎中的价值优于C3、血浆C4d、Bb、C5 b-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性的敏感指标,并且在常规测量不起作用的情况下可能最有帮助,例如在尽管有临床疾病活动性的证据但C3和C4水平保持正常的狼疮患者中,从这项研究中似乎可以看出,检测尿C3 d可能是测量狼疮肾病背景下补体激活的简单方法,用于临床疾病活动性测量的仪器(例如SLAM和SLEDAI)的可用性可以使得能够更一致地定义狼疮疾病活动性,并且因此可以提供用于更好地检查补体激活产物在预测较大患者群体中的狼疮疾病活动性中的作用的手段。
Objective. 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.Methods. Lupus disease activity,vas 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 microsassay 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.Results. 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).Conclusion. 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.