Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
World J Gastroenterol. 2021 Jan 7;27(1):92-106. doi: 10.3748/wjg.v27.i1.92.
Infantile-onset inflammatory bowel disease (IO-IBD) occurs in very young children and causes severe clinical manifestations, which has poor responses to traditional inflammatory bowel disease (IBD) treatments. At present, there are no simple and reliable laboratory indicators for early screening IO-IBD patients, especially those in whom the disease is caused by monogenic diseases.
To search for valuable indicators for early identifying IO-IBD patients, especially those in whom the disease is caused by monogenic diseases.
A retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years. Based on the next-generation sequencing results, they were divided into a monogenic IBD group (M-IBD) and a non-monogenic IBD group (NM-IBD). Forty age-matched patients with allergic proctocolitis (AP) were included in a control group. The clinical manifestations and the inflammatory factors in peripheral blood were evaluated. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to identify the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD, respectively.
Among the 44 M-IBD patients, 35 carried mutations, and the most common mutations were c.301C>T (p.R101W, 30/70) and the c.537G>A (p.T179T, 17/70). Patients with higher serum tumor necrosis factor (TNF)-α value were more likely to have IBD [odds ratio (OR) = 1.25, 95% confidence interval (CI): 1.05-1.50, = 0.013], while higher serum albumin level was associated with lower risk of IBD (OR = 0.86, 95%CI: 0.74-1.00, = 0.048). The cut-off values of TNF-α and albumin were 17.40 pg/mL (sensitivity: 0.78; specificity: 0.88) and 36.50 g/L (sensitivity: 0.80; specificity: 0.90), respectively. The increased ferritin level was indicative of a genetic mutation in IO-IBD patients. Its cut-off value was 28.20 ng/mL (sensitivity: 0.93; specificity: 0.92). When interleukin (IL)-10 level was higher than 33.05 pg/mL (sensitivity: 1.00; specificity: 0.84), or the onset age was earlier than 0.21 mo (sensitivity: 0.82; specificity: 0.94), the presence of disease-causing mutations in in IO-IBD patients was strongly suggested.
Serum TNF-α and albumin level could differentiate IO-IBD patients from allergic proctocolitis patients, and serum ferritin and IL-10 levels are useful indicators for early diagnosing monogenic IO-IBD.
婴儿期起病的炎症性肠病（IO-IBD）发生于非常年幼的儿童，引起严重的临床表现，对传统的炎症性肠病（IBD）治疗反应不佳。目前，对于 IO-IBD 患者，特别是那些由单基因疾病引起的患者，尚无简单可靠的实验室指标进行早期筛查。
寻找有价值的指标，以早期识别 IO-IBD 患者，特别是那些由单基因疾病引起的患者。
对过去 5 年我院收治的 73 例 IO-IBD 患儿进行回顾性分析。根据下一代测序结果，将其分为单基因 IBD 组（M-IBD）和非单基因 IBD 组（NM-IBD）。纳入 40 例年龄匹配的过敏性结肠炎（AP）患儿作为对照组。评估其临床表现和外周血炎症因子。采用 logistic 回归分析和受试者工作特征（ROC）曲线分析，分别识别 IO-IBD 及单基因 IO-IBD 的筛查因素及截断值。
在 44 例 M-IBD 患儿中，35 例携带 突变，最常见的突变是 c.301C>T（p.R101W，30/70）和 c.537G>A（p.T179T，17/70）。血清肿瘤坏死因子（TNF）-α值较高的患者更有可能患有 IBD[比值比（OR）=1.25，95%置信区间（CI）：1.05-1.50， = 0.013]，而血清白蛋白水平较高与 IBD 风险较低相关（OR=0.86，95%CI：0.74-1.00， = 0.048）。TNF-α和白蛋白的截断值分别为 17.40 pg/mL（灵敏度：0.78；特异性：0.88）和 36.50 g/L（灵敏度：0.80；特异性：0.90）。铁蛋白水平升高提示 IO-IBD 患者存在基因突变。其截断值为 28.20 ng/mL（灵敏度：0.93；特异性：0.92）。当白细胞介素（IL）-10 水平高于 33.05 pg/mL（灵敏度：1.00；特异性：0.84）或发病年龄早于 0.21 个月（灵敏度：0.82；特异性：0.94）时，强烈提示 IO-IBD 患者存在 基因突变。
血清 TNF-α和白蛋白水平可区分 IO-IBD 患者和过敏性结肠炎患者，血清铁蛋白和 IL-10 水平是早期诊断单基因 IO-IBD 的有用指标。
