Agardh Daniel, Lee Hye-Seung, Kurppa Kalle, Simell Ville, Aronsson Carin Andrén, Jörneus Ola, Hummel Michael, Liu Edwin, Koletzko Sibylle
The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden; Pediatric Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida;
Pediatric Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida;
Pediatrics. 2015 Apr;135(4):627-34. doi: 10.1542/peds.2014-3675. Epub 2015 Mar 2.
To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort.
Children from 6 clinical centers in 4 countries positive for HLA-DR3-DQ2 or DR4-DQ8 were annually screened for tissue transglutaminase antibodies (tTGA) and assessed for symptoms by questionnaires. Associations of symptoms with anthropometrics, known risk factors for CD, tTGA levels, and mucosal lesions in those biopsied were examined.
Of 6706 screened children, 914 developed persistent positive tTGA, 406 underwent biopsies, and 340 had CD. Compared with age-matched tTGA-negative children, those with persistent tTGA were more likely to have symptoms at 2 (34% vs 19%, P < .001) and 3 years of age (28% vs 19%, P = .009) but not at 4 years (27% vs 21%, NS). Z-scores for height, weight, and BMI did not differ between groups. In children with persistent tTGA, having ≥ 1 symptom was associated with family history of CD (odds ratio = 2.59, 95% confidence interval, 1.21-5.57) but not with age, gender, or HLA-DR3-DQ2 homozygosity. At seroconversion, tTGA levels were higher in symptomatic than asymptomatic children (P < .001), in those from CD families (P < .001), and in US participants (P < .001) but not associated with age, gender, or HLA genotype. tTGA levels correlated with severity of mucosal lesions both in symptomatic (r = 0.53, P < .001) and asymptomatic children (r = 0.22, P = .01).
A majority of children detected with persistent tTGA in screenings are asymptomatic and have normal growth by age 4 years. tTGA levels correlate more strongly with severity of mucosal lesions in symptomatic as compared with asymptomatic children.
在一个具有遗传风险的出生队列中,研究乳糜泻(CD)的临床特征及其与CD风险因素的关联。
来自4个国家6个临床中心的携带HLA-DR3-DQ2或DR4-DQ8阳性的儿童每年接受组织转谷氨酰胺酶抗体(tTGA)筛查,并通过问卷评估症状。研究了症状与人体测量学、已知的CD风险因素、tTGA水平以及活检者的黏膜病变之间的关联。
在6706名接受筛查的儿童中,914名tTGA持续呈阳性,406名接受了活检,340名患有CD。与年龄匹配的tTGA阴性儿童相比,tTGA持续阳性的儿童在2岁(34%对19%,P<.001)和3岁时(28%对19%,P=.009)更有可能出现症状,但在4岁时没有差异(27%对21%,无显著性差异)。两组之间身高、体重和BMI的Z评分没有差异。在tTGA持续阳性儿童中,有≥1种症状与CD家族史相关(比值比=2.59,95%置信区间,1.21-5.57),但与年龄、性别或HLA-DR3-DQ2纯合性无关。在血清转化时,有症状儿童的tTGA水平高于无症状儿童(P<.001),CD家族儿童(P<.001)以及美国参与者(P<.001),但与年龄、性别或HLA基因型无关。tTGA水平与有症状儿童(r=0.53,P<.001)和无症状儿童(r=0.22,P=.01)的黏膜病变严重程度均相关。
在筛查中检测到tTGA持续阳性的大多数儿童无症状,到4岁时生长正常。与无症状儿童相比,tTGA水平与有症状儿童的黏膜病变严重程度相关性更强。