Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus
Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus
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DOI：
10.1002/art.20980
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发表时间：
2005-04-01
影响因子：
--
通讯作者：
Joh, T
中科院分区：
文献类型：
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作者：
Linnik, MD;Hu, JZ;Joh, T
Objective.利用2项随机对照试验的数据，探讨系统性红斑狼疮（SLE）患者抗双链DNA（anti-dsDNA）抗体水平变化与肾脏疾病发作风险之间的关系。分析基于487例SLE患者和狼疮肾炎病史，基线时抗dsDNA抗体滴度>= 15 IU/ml，通过Farr测定。结果显示了合并的患者人群、安慰剂组和药物治疗组，其中使用了基于dsDNA的生物缀合物（阿贝替莫司钠; LJP 394）。抗dsDNA抗体水平的变化与C3水平的变化呈负相关（两项试验中P < 0.0001）。考克斯比例风险回归模型显示，抗dsDNA抗体水平的变化与肾耀斑的风险相关。该模型预测，抗dsDNA抗体水平降低50%的点估计值分别与2项试验中肾耀斑风险降低52%（95%置信区间[95% CI] 26- 68%，标称P = 0.0007）和53%（95% CI 33- 69%，标称P < 0.0001）相关。在这2项试验中，抗dsDNA抗体持续下降的患者（分别为3.0%和4.1%）的肾闪辉发生率低于抗体水平稳定或升高的患者（分别为21.3%和20.3%）。抗双链DNA抗体水平的变化与肾耀斑的风险直接相关，与C3水平的变化呈负相关。降低抗dsDNA抗体水平可能代表狼疮性肾炎SLE患者的治疗目标，因为它与降低肾耀斑的风险有关。
Objective. To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials.Methods. Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer >= 15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used.Results. Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26-68%, nominal P = 0.0007) and a 53% reduction (95% CI 33-69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively).Conclusion. Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.