Atkinson Meredith A, Leonard Mary B, Herskovitz Rita, Baldassano Robert N, Denburg Michelle R
Department of Pediatrics, Division of Pediatric Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Pediatrics and Medicine, Division of Nephrology, Stanford University School of Medicine, Stanford, CA.
J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):90-94. doi: 10.1097/MPG.0000000000001650.
Anemia is the most common systemic complication of inflammatory bowel disease, is more common in affected children than in adults, and is mediated in large part by chronic inflammation. Inflammation increases levels of the iron-regulatory protein hepcidin, which have been elevated in adults with Crohn disease.
We measured serum hepcidin-25 and hemoglobin (Hgb) in 40 children and adolescents with Crohn disease at baseline and 10 weeks after initiation of anti-tumor necrosis factor (TNF)-α therapy. Measures of disease activity, inflammatory markers, and cytokines were obtained in all subjects. Anemia was defined by World Health Organization criteria.
At baseline hepcidin and C-reactive protein levels were correlated, and 95% of subjects were anemic. After anti-TNF-α therapy, median (interquartile range) hepcidin concentrations decreased significantly and the distribution narrowed (27.9 [16.2, 52.9] vs 23.2 [11.1, 37.7] ng/mL, P = 0.01). Mean (standard deviation) Hgb also increased significantly (10.6 ± 1.2 to 10.9 ± 1.1 g/dL, P = 0.02), and the increase was sustained at 12 months, although 90% of participants continued to meet anemia criteria at 10 weeks. Disease activity and markers of inflammation also decreased and albumin levels increased. In generalized estimating equation analyses, higher TNF-α, interleukin 6, erythrocyte sedimentation rate, and C-reactive protein were associated with higher hepcidin concentrations (P = 0.04, P = 0.03, P = 0.003, and P < 0.001, respectively), and increased levels of disease activity were associated with higher hepcidin.
In children with Crohn disease, anti-TNF-α therapy is associated with decreased levels of hepcidin and increased Hgb 10 weeks after induction. Improvement in anemia may be a secondary benefit for children who receive this therapy.
贫血是炎症性肠病最常见的全身并发症，在患病儿童中比成人更常见，且在很大程度上由慢性炎症介导。炎症会增加铁调节蛋白铁调素的水平，在克罗恩病成人患者中该蛋白水平已升高。
我们在40例克罗恩病儿童和青少年患者基线时以及开始抗肿瘤坏死因子（TNF）-α治疗10周后测量了血清铁调素-25和血红蛋白（Hgb）。对所有受试者进行了疾病活动度、炎症标志物和细胞因子的检测。贫血按照世界卫生组织标准定义。
基线时铁调素和C反应蛋白水平相关，95%的受试者存在贫血。抗TNF-α治疗后，铁调素浓度中位数（四分位间距）显著降低且分布变窄（27.9 [16.2, 52.9] 对23.2 [11.1, 37.7] ng/mL，P = 0.01）。平均（标准差）Hgb也显著升高（10.6 ± 1.2至10.9 ± 1.1 g/dL，P = 0.02），且在12个月时仍持续升高，尽管90%的参与者在10周时仍符合贫血标准。疾病活动度和炎症标志物也降低，白蛋白水平升高。在广义估计方程分析中，较高的TNF-α、白细胞介素6、红细胞沉降率和C反应蛋白与较高的铁调素浓度相关（分别为P = 0.04、P = 0.03、P = 0.003和P < 0.001），且疾病活动度增加与较高的铁调素相关。
在克罗恩病儿童中，抗TNF-α治疗与诱导治疗10周后铁调素水平降低和Hgb升高相关。贫血改善可能是接受该治疗儿童的次要获益。
