Soendergaard Christoffer, Nielsen Ole Haagen, Seidelin Jakob Benedict, Kvist Peter Helding, Bjerrum Jacob Tveiten
*Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark; and †Department of Histology, Novo Nordisk A/S, Maaloev, Denmark.
Inflamm Bowel Dis. 2015 May;21(5):1077-88. doi: 10.1097/MIB.0000000000000348.
Initial assessment of patients with ulcerative colitis (UC) is challenging and relies on apparent clinical symptoms and measurements of surrogate markers (e.g., C-reactive protein [CRP] or similar acute phase proteins). As CRP only reliably identifies patients with severe disease, novel biomarkers are currently needed for identification of patients with mild or moderate disease activity. Using a commercially available platform, we aimed at identifying serum biomarkers that are able to grade the disease severity.
Serum samples from 65 patients with UC with varying disease activity (Mayo score) and from 40 healthy controls were analyzed by multiplex enzyme-linked immunosorbent assay for 78 potential disease biomarkers. Using the statistical software SIMCA-P+ and GraphPad Prism, multivariate statistical analyses were conducted to identify a limited number of biomarkers to assess disease severity.
Alpha-1 antitrypsin (AAT) differentiated between mild and moderate UC (area under the curve [AUC] = 0.79) with a sensitivity of 0.90 and a specificity of 0.70, thereby exceeding the predictive ability of CRP (AUC = 0.52). Combining alpha-1 antitrypsin and granulocyte colony-stimulating factor produced a predictive model with an AUC of 0.72 when differentiating mild and moderate UC, and an AUC of 0.96 when differentiating moderate and severe UC, the latter being as reliable as CRP.
Alpha-1 antitrypsin is identified as a potential serum biomarker of mild-to-moderate disease activity in UC. With the ability to differentiate between mild, moderate, and severe stages of UC using a simple serum biomarker that is already commercially available, clinicians can initiate individualized treatment regimens at an earlier stage before endoscopic examinations are available.
对溃疡性结肠炎(UC)患者的初始评估具有挑战性,依赖于明显的临床症状和替代标志物(如C反应蛋白[CRP]或类似的急性期蛋白)的测量。由于CRP仅能可靠地识别重症患者,目前需要新的生物标志物来识别轻度或中度疾病活动的患者。我们旨在利用一个商业可用平台识别能够对疾病严重程度进行分级的血清生物标志物。
采用多重酶联免疫吸附测定法对65例疾病活动度不同(梅奥评分)的UC患者和40例健康对照的血清样本进行78种潜在疾病生物标志物的分析。使用统计软件SIMCA-P+和GraphPad Prism进行多变量统计分析,以识别数量有限的用于评估疾病严重程度的生物标志物。
α-1抗胰蛋白酶(AAT)在轻度和中度UC之间具有鉴别能力(曲线下面积[AUC]=0.79),敏感性为0.90,特异性为0.70,从而超过了CRP的预测能力(AUC=0.52)。将α-1抗胰蛋白酶和粒细胞集落刺激因子结合,在区分轻度和中度UC时产生的预测模型AUC为0.72,在区分中度和重度UC时AUC为0.96,后者与CRP一样可靠。
α-1抗胰蛋白酶被确定为UC中轻度至中度疾病活动的潜在血清生物标志物。通过使用一种已商业化的简单血清生物标志物能够区分UC的轻度、中度和重度阶段,临床医生可以在内镜检查之前更早阶段启动个体化治疗方案。