高危家族儿童乳糜泻发病预测模型：预防 CD 队列研究数据。
Prediction Models for Celiac Disease Development in Children From High-Risk Families: Data From the PreventCD Cohort.
机构信息
Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.
Translational Medical Sciences and European Laboratory for the Investigation of Food-Induced Disease, University of Naples Federico II, Naples, Italy.
出版信息
Gastroenterology. 2022 Aug;163(2):426-436. doi: 10.1053/j.gastro.2022.04.030. Epub 2022 Apr 26.
BACKGROUND & AIMS: Screening for celiac disease (CD) is recommended in children with affected first-degree relatives (FDR). However, the frequency of screening and at what age remain unknown. The aims of this study were to detect variables influencing the risk of CD development and develop and validate clinical prediction models to provide individualized screening advice.
METHODS
We analyzed prospective data from the 10 years of follow-up of the PreventCD-birth cohort involving 944 genetically predisposed children with CD-FDR. Variables significantly influencing the CD risk were combined to determine a risk score. Landmark analyses were performed at different ages. Prediction models were created using multivariable Cox proportional hazards regression analyses, backward elimination, and Harrell's c-index for discrimination. Validation was done using data from the independent NeoCel cohort.
RESULTS
In March 2019, the median follow-up was 8.3 years (22 days-12.0 years); 135/944 children developed CD (mean age, 4.3 years [range, 1.1-11.4]). CD developed significantly more often in girls (P = .005) and in Human Leukocyte Antigen (HLA)-DQ2 homozygous individuals (8-year cumulative incidence rate of 35.4% vs maximum of the other HLA-risk groups 18.2% [P < .001]). The effect of homozygosity DR3-DQ2/DR7-DQ2 on CD development was only present in girls (interaction P = .04). The prediction models showed good fit in the validation cohort (Cox regression 0.81 [0.54]). To calculate a personalized risk of CD development and provide screening advice, we designed the Prediction application https://hputter.shinyapps.io/preventcd/.
CONCLUSION
Children with CD-FDR develop CD early in life, and their risk depends on gender, age and HLA-DQ, which are all factors that are important for sound screening advice. These children should be screened early in life, including HLA-DQ2/8-typing, and if genetically predisposed to CD, they should get further personalized screening advice using our Prediction application.
TRIAL REGISTRATION NUMBER
ISRCTN74582487 (https://www.isrctn.com/search?q=ISRCTN74582487).
背景与目的
建议对有一级亲属（FDR）受累的乳糜泻（CD）患儿进行 CD 筛查。然而，筛查的频率和年龄尚不清楚。本研究旨在发现影响 CD 发病风险的变量，并建立和验证临床预测模型，为个体化筛查提供建议。
方法
我们分析了前瞻性的、包含 944 名具有 CD-FDR 遗传易感性的儿童的 PreventCD-birth 队列 10 年随访的数据。将显著影响 CD 风险的变量组合起来确定风险评分。在不同的年龄进行里程碑分析。使用多变量 Cox 比例风险回归分析、向后消除和 Harrell's c 指数进行判别来建立预测模型。使用独立的 NeoCel 队列的数据进行验证。
结果
2019 年 3 月，中位随访时间为 8.3 年（22 天-12.0 年）；944 例儿童中有 135 例（平均年龄 4.3 岁[范围 1.1-11.4 岁]）发生 CD。女孩中 CD 的发病显著更常见（P=0.005），HLA-DQ2 纯合子个体（8 年累积发生率为 35.4%，而其他 HLA 风险组最高为 18.2%[P<0.001]）。DR3-DQ2/DR7-DQ2 纯合子对 CD 发病的影响仅见于女孩（交互 P=0.04）。预测模型在验证队列中的拟合度较好（Cox 回归 0.81[0.54]）。为了计算 CD 发病的个体化风险并提供筛查建议，我们设计了 Prediction 应用程序 https://hputter.shinyapps.io/preventcd/。
结论
有 CD-FDR 的儿童在生命早期即发生 CD，其发病风险取决于性别、年龄和 HLA-DQ，这些都是制定合理筛查建议的重要因素。这些儿童应在生命早期进行筛查，包括 HLA-DQ2/8 型鉴定，如果遗传易患 CD，则应使用我们的 Prediction 应用程序进一步进行个体化筛查建议。
注册号
ISRCTN74582487（https://www.isrctn.com/search?q=ISRCTN74582487）。
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