Serum levels of autoantibodies against C-reactive protein correlate with renal disease activity and response to therapy in lupus nephritis.
Serum levels of autoantibodies against C-reactive protein correlate with renal disease activity and response to therapy in lupus nephritis.
复制标题
DOI：
10.1186/ar2880
复制
发表时间：
2009
影响因子：
4.9
通讯作者：
Gunnarsson I
中科院分区：
文献类型：
--
作者：
Sjöwall C;Zickert A;Skogh T;Wetterö J;Gunnarsson I
血清C反应蛋白(CRP)水平很少反映系统性红斑狼疮(SLE)的疾病活动性。我们以前已经证明，针对CRP新表位的自身抗体经常出现在SLE中，但这并不能解释在斑块中看到的适度的CRP反应。然而，我们反复发现抗-CRP水平与狼疮性疾病的活动性平行，在有肾脏受累的患者中水平最高；因此，我们的目标是研究狼疮性肾炎患者的抗-CRP。纳入狼疮性肾炎患者38例。激素联合环磷酰胺、霉酚酸酯或利妥昔单抗治疗在基线肾活检后开始。在≥后6个月进行第二次活检。两组患者均进行血肌酐、胱抑素C、补体、抗双链DNA、抗C反应蛋白及尿液分析。根据世界卫生组织(WHO)的级别以及活动性和慢性化指数对活检进行评估。使用不列颠群岛狼疮评估组织(BILAG)指数评估肾脏疾病活动性。基线时，34/38例患者肾脏BILAG-A；4/38例BILAG-B。基线活检显示WHO III级肾炎8例，IV级肾炎19例，III~IV/V级肾炎3例，V级肾炎8例。38例患者中有17例在基线时抗-CRP阳性，6例在随访时呈阳性。总体而言，抗-C-反应蛋白水平在随访时下降(P<；0.0001)，且抗-C-反应蛋白水平与肾脏BILAG相关(r=0.29，P=0.012)。根据肾脏BILAG判断，基线时抗-CRP阳性检测优于抗-dsDNA和C1q检测来预测治疗反应差。基线抗C反应蛋白水平与肾活检活动性相关(r=0.33，P=0.045)，与慢性化指数无关。抗-C反应蛋白水平与抗双链DNA呈正相关(荧光增强免疫分析：r=0.63，P=0.0003；荧光镜检：r=0.44，P<；0.0001)，与补体C3(r=0.35，P=0.007)、补体4(r=0.29，P=0.02)呈负相关，与补体C1q无相关性(r=0.14，P=0.24)。未发现与尿液成分、肌酐、胱抑素C或肾小球滤过率相关。在目前的研究中，我们发现狼疮性肾炎患者的抗-CRP水平与组织病理学活动性之间存在统计学上的显著相关性，而基线抗-CRP检测阳性则预示着治疗效果不佳。我们的数据也证实了先前的发现，即抗-CRP与疾病活动性之间存在关联。这表明抗-CRP有助于评估SLE肾炎的疾病活动性和治疗反应，并强调了抗-CRP抗体在狼疮性肾炎中起致病作用的假说。
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 ≥ 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.
登录
查看更多内容
影响因子：
37.8
作者：
Li, SH;Szmitko, PE;Verma, S
通讯作者：
Verma, S
影响因子：
--
作者：
Enocsson, Helena;Sjowall, Christopher;Wettero, Jonas
通讯作者：
Wettero, Jonas
影响因子：
27.4
作者：
Bootsma, H;Spronk, PE;Kallenberg, CGM
通讯作者：
Kallenberg, CGM
影响因子：
5.5
作者：
Gordon, C;Sutcliffe, N;Isenberg, DA
通讯作者：
Isenberg, DA
影响因子：
20.1
作者：
Eisenhardt, Steffen U.;Habersberger, Jonathon;Peter, Karlheinz
通讯作者：
Peter, Karlheinz