Rheumatology/AIR, Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden.
Arthritis Res Ther. 2009;11(6):R188. doi: 10.1186/ar2880. Epub 2009 Dec 11.
Serum levels of C-reactive protein (CRP) seldom reflect disease activity in systemic lupus erythematosus (SLE). We have previously shown that autoantibodies against neo-epitopes of CRP often occur in SLE, but that this does not explain the modest CRP response seen in flares. However, we have repeatedly found that anti-CRP levels parallel lupus disease activity, with highest levels in patients with renal involvement; thus, we aimed to study anti-CRP in a material of well-characterized lupus nephritis patients.
Thirty-eight patients with lupus nephritis were included. Treatment with corticosteroids combined with cyclophosphamide, mycophenolate mofetil or rituximab was started after baseline kidney biopsy. A second biopsy was taken after > or = 6 months. Serum creatinine, cystatin C, complement, anti-dsDNA, anti-CRP and urinalysis were done on both occasions. Biopsies were evaluated regarding World Health Organisation (WHO) class and indices of activity and chronicity. Renal disease activity was estimated using the British Isles Lupus Assessment Group (BILAG) index.
At baseline, 34/38 patients had renal BILAG-A; 4/38 had BILAG-B. Baseline biopsies showed WHO class III (n = 8), IV (n = 19), III to IV/V (n = 3) or V (n = 8) nephritis. Seventeen out of 38 patients were anti-CRP-positive at baseline, and six at follow-up. Overall, anti-CRP levels had dropped at follow-up (P < 0.0001) and anti-CRP levels correlated with renal BILAG (r = 0.29, P = 0.012). A positive anti-CRP test at baseline was superior to anti-dsDNA and C1q in predicting poor response to therapy as judged by renal BILAG. Baseline anti-CRP levels correlated with renal biopsy activity (r = 0.33, P = 0.045), but not with chronicity index. Anti-CRP levels were positively correlated with anti-dsDNA (fluorescence-enhanced immunoassay: r = 0.63, P = 0.0003; Crithidia luciliae immunofluorescence microscopy test: r = 0.44, P < 0.0001), and inversely with C3 (r = 0.35, P = 0.007) and C4 (r = 0.29, P = 0.02), but not with C1q (r = 0.14, P = 0.24). No associations with urinary components, creatinine, cystatin C or the glomerular filtration rate were found.
In the present study, we demonstrate a statistically significant correlation between anti-CRP levels and histopathological activity in lupus nephritis, whereas a baseline positive anti-CRP test predicted poor response to therapy. Our data also confirm previous findings of associations between anti-CRP and disease activity. This indicates that anti-CRP could be helpful to assess disease activity and response to therapy in SLE nephritis, and highlights the hypothesis of a pathogenetic role for anti-CRP antibodies in lupus nephritis.
血清 C 反应蛋白（CRP）水平很少反映系统性红斑狼疮（SLE）的疾病活动度。我们之前已经表明，针对 CRP 新表位的自身抗体通常在 SLE 中出现，但这并不能解释 flares 中 CRP 反应的适度性。然而，我们反复发现抗 CRP 水平与狼疮疾病活动度平行，在有肾脏受累的患者中水平最高；因此，我们旨在研究在特征明确的狼疮肾炎患者的材料中抗 CRP 的情况。
纳入 38 例狼疮肾炎患者。在基线肾脏活检后，开始使用皮质类固醇联合环磷酰胺、吗替麦考酚酯或利妥昔单抗治疗。在 > 或 = 6 个月后进行第二次活检。在两次检查时都进行了血清肌酐、胱抑素 C、补体、抗 dsDNA、抗 CRP 和尿分析。根据世界卫生组织（WHO）分类以及活动和慢性指数对活检进行评估。使用不列颠群岛狼疮评估组（BILAG）指数估计肾脏疾病活动度。
基线时，38 例患者中有 34 例有肾脏 BILAG-A；4 例有 BILAG-B。基线活检显示 III 级（n = 8）、IV 级（n = 19）、III 至 IV/V 级（n = 3）或 V 级（n = 8）肾炎。38 例患者中有 17 例在基线时抗 CRP 阳性，6 例在随访时阳性。总体而言，抗 CRP 水平在随访时下降（P < 0.0001），并且抗 CRP 水平与肾脏 BILAG 相关（r = 0.29，P = 0.012）。基线时抗 CRP 阳性试验在预测肾脏 BILAG 判断的治疗反应不佳方面优于抗 dsDNA 和 C1q。基线抗 CRP 水平与肾脏活检活动度相关（r = 0.33，P = 0.045），但与慢性指数无关。抗 CRP 水平与抗 dsDNA 呈正相关（荧光增强免疫测定：r = 0.63，P = 0.0003；克氏锥虫免疫荧光显微镜试验：r = 0.44，P < 0.0001），与 C3 呈负相关（r = 0.35，P = 0.007），与 C4 呈负相关（r = 0.29，P = 0.02），但与 C1q 无关（r = 0.14，P = 0.24）。未发现与尿成分、肌酐、胱抑素 C 或肾小球滤过率有关的关联。
在本研究中，我们证明了抗 CRP 水平与狼疮肾炎的组织病理学活动之间存在统计学显著相关性，而基线时抗 CRP 阳性试验预测了治疗反应不佳。我们的数据还证实了之前关于抗 CRP 与疾病活动之间关联的发现。这表明抗 CRP 可有助于评估 SLE 肾炎的疾病活动度和治疗反应，并强调了抗 CRP 抗体在狼疮肾炎发病机制中的假说。
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