Centre for Rheumatology Research, University College London, Windeyer Institute, 46 Cleveland Street, London W1T 4JF, UK.
Arthritis Res Ther. 2009 Oct 14;11(5):R154. doi: 10.1186/ar2831.
Glomerulonephritis is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Deposition of autoantibodies in the glomeruli plays a key role in the development of lupus nephritis (LN). Different groups have proposed that either anti-nucleosome antibodies or antibodies that bind the intrinsic renal antigen, alpha-actinin, are central to the pathogenesis of LN. These theories have been based mainly on cross-sectional studies in patients and on experiments in animal models. No previous longitudinal studies have compared the relationships between levels of these antibodies and markers of renal function. We assessed how well anti-alpha-actinin, anti-nucleosome and anti-double-stranded DNA (anti-dsDNA) antibodies reflected renal outcome measures in patients with new-onset LN followed for up to 2 years.
Renal disease activity was monitored by measuring urine protein/creatinine ratio (PCR), serum albumin and a composite outcome of renal remission. At each time point, anti-nucleosome and anti-alpha-actinin antibodies were measured by enzyme-linked immunosorbent assay. High-avidity anti-dsDNA antibodies were measured using the Farrzyme assay. We analysed relationships between levels of the three antibodies and between antibody levels and renal outcome measures over time.
Levels of anti-nucleosome and anti-dsDNA were positively correlated with each other (r = 0.6, P = 0.0001) but neither correlated with anti-alpha-actinin level. At baseline, mean anti-nucleosome levels were higher in patients with LN than in healthy controls (0.32 versus 0.01, P < 0.001). The same was true for anti-dsDNA antibodies (0.50 versus 0.07, P < 0.001) but not for anti-alpha-actinin (0.33 versus 0.29). Over the follow-up period, anti-nucleosome and anti-dsDNA levels associated positively with urine PCR (P = 0.041 and 0.051, respectively) and negatively with serum albumin (P = 0.027 and 0.032, respectively). Both anti-nucleosome and anti-dsDNA levels were significantly lower during renal remission than when renal disease was active (P = 0.002 and 0.003, respectively). However, there was no relationship between anti-alpha-actinin levels and urine PCR, serum albumin or remission status.
This prospective longitudinal clinical study is the first to compare levels of anti-nucleosome, anti-dsDNA and anti-alpha-actinin antibodies in the same patients with SLE. Our results support the concept that, in the majority of patients, anti-nucleosome antibodies play a major role in pathogenesis of LN, in contrast to anti-alpha-actinin antibodies.
肾小球肾炎是红斑狼疮（SLE）患者发病率和死亡率的主要原因。自身抗体在肾小球中的沉积在狼疮肾炎（LN）的发病机制中起着关键作用。不同的研究组提出，抗核小体抗体或与内在肾抗原α-辅肌动蛋白结合的抗体，是 LN 发病机制的核心。这些理论主要基于对患者的横断面研究和动物模型实验。以前没有进行过比较这些抗体水平与肾功能标志物之间关系的纵向研究。我们评估了在新诊断的 LN 患者中，抗α-辅肌动蛋白、抗核小体和抗双链 DNA（抗 dsDNA）抗体在长达 2 年的随访期间对肾脏结局测量的反映程度。
通过测量尿蛋白/肌酐比（PCR）、血清白蛋白和肾脏缓解的综合结局来监测肾脏疾病活动度。在每个时间点，通过酶联免疫吸附试验测量抗核小体和抗α-辅肌动蛋白抗体。使用 Farrzyme 测定法测量高亲和力抗 dsDNA 抗体。我们分析了三种抗体之间的水平关系以及随时间变化的抗体水平与肾脏结局测量之间的关系。
抗核小体和抗 dsDNA 水平相互之间呈正相关（r = 0.6，P = 0.0001），但均与抗α-辅肌动蛋白水平无关。在基线时，LN 患者的抗核小体水平高于健康对照组（0.32 比 0.01，P < 0.001）。抗 dsDNA 抗体也是如此（0.50 比 0.07，P < 0.001），但抗α-辅肌动蛋白抗体并非如此（0.33 比 0.29）。在随访期间，抗核小体和抗 dsDNA 水平与尿 PCR 呈正相关（P = 0.041 和 0.051），与血清白蛋白呈负相关（P = 0.027 和 0.032）。在肾脏缓解期间，抗核小体和抗 dsDNA 水平均显著低于肾脏疾病活动期（P = 0.002 和 0.003）。然而，抗α-辅肌动蛋白水平与尿 PCR、血清白蛋白或缓解状态之间没有关系。
这项前瞻性纵向临床研究首次在同一 SLE 患者中比较了抗核小体、抗 dsDNA 和抗α-辅肌动蛋白抗体的水平。我们的结果支持这样一种观点，即在大多数患者中，抗核小体抗体在 LN 的发病机制中起着主要作用，而不是抗α-辅肌动蛋白抗体。
Zotero 插件
