真正的乳糜泻患者请站出来？德国 LIFE 儿童研究中的乳糜泻患病率。

Will the Real Coeliac Disease Please Stand Up? Coeliac Disease Prevalence in the German LIFE Child Study.

机构信息

Department of Women and Child Health, University Hospital for Children and Adolescents and Center for Pediatric Research.

Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics.

出版信息

J Pediatr Gastroenterol Nutr. 2018 Oct;67(4):494-500. doi: 10.1097/MPG.0000000000002052.

DOI:10.1097/MPG.0000000000002052

PMID:29901554

Abstract

OBJECTIVES

Assessing the seroprevalence and the prevalence of definite coeliac disease (CD) in the German LIFE Child Health study cohort including immunoglobulin A (IgA) antibodies against tissue transglutaminase (IgA-TTG) in addition to IgG antibodies against deamidated gliadin peptides (IgG-DGP) and human leukocyte antigen (HLA)-DQ2/8 genotyping.

METHODS

Samples from children and adolescents were first screened for IgA-TTG and IgG-DGP. If IgA-TTG was above 0.5 times the upper limit of normal and/or IgG-DGP was positive, IgA antibodies against endomysium (IgA-EmA) were measured, and HLA was genotyped. In patients with only IgG-DGP positivity, total IgA was assayed. Subjects with suspicious results were followed up serologically and, in case of repeatedly positive antibody results, invited for a personal interview. Further diagnostic data were obtained independent from our study.

RESULTS

We screened 2363 children's blood samples collected from 2011 to 2015. The seroprevalence, that is, IgA-TTG and/or IgA-EmA positivity or IgG-DGP positivity with IgA <0.05 g/L, was 1.57% (95% confidence interval [CI95%] 1.14-2.15). The prevalence of suspected CD, that is, seroprevalence and compatible HLA genotype with hitherto unknown mucosal damage, was 1.35% (CI95% 0.96-1.91). Definite CD, that is, seropositivity accompanied by positive intestinal biopsy or IgA-TTG ≥ 10 × upper limit of normal, was found in 0.42% (CI95% 0.22-0.80). Seven children claimed to have CD. The HLA haplotype, however, matched in only 4 of them resulting in an overall CD prevalence of at least 0.59% (CI95% 0.34-1.02). Thirteen unclear cases remained; therefore, the prevalence may even be higher.

CONCLUSIONS

The prevalence of definite CD in a population-representative German cohort is higher than previously described. HLA-DQ typing is helpful to identify false-positive IgA-TTG patients negative for IgA-EmA and/or IgG-DGP under screening conditions and unmasks possible misdiagnoses of CD.

摘要

目的

在德国 LIFE 儿童健康研究队列中评估血清流行率和明确的乳糜泻（CD）患病率，该队列包括针对组织转谷氨酰胺酶（IgA-TTG）的免疫球蛋白 A（IgA）抗体，以及针对脱酰胺的麦胶肽（IgG-DGP）和人类白细胞抗原（HLA）-DQ2/8 基因分型的 IgG 抗体。

方法

首先对儿童和青少年的样本进行 IgA-TTG 和 IgG-DGP 筛查。如果 IgA-TTG 高于正常上限的 0.5 倍且/或 IgG-DGP 阳性，则测量针对内肌层的 IgA 抗体（IgA-EmA），并进行 HLA 基因分型。对于仅 IgG-DGP 阳性的患者，检测总 IgA。对可疑结果的患者进行血清学随访，如果抗体结果反复阳性，则邀请他们进行个人访谈。从我们的研究中获得了进一步的诊断数据。

结果

我们对 2011 年至 2015 年采集的 2363 名儿童的血液样本进行了筛查。血清流行率，即 IgA-TTG 和/或 IgA-EmA 阳性或 IgG-DGP 阳性且 IgA<0.05 g/L，为 1.57%（95%置信区间 [CI95%] 1.14-2.15）。可疑 CD 的患病率，即血清流行率和未知黏膜损伤的相容 HLA 基因型，为 1.35%（95%置信区间 [CI95%] 0.96-1.91）。明确的 CD，即血清阳性伴阳性肠活检或 IgA-TTG≥10×正常上限，占 0.42%（95%置信区间 [CI95%] 0.22-0.80）。有 7 名儿童声称患有 CD。然而，仅在其中 4 名患者中匹配 HLA 单倍型，导致至少 0.59%（95%置信区间 [CI95%] 0.34-1.02）的总体 CD 患病率。还有 13 例不明确的病例，因此患病率可能更高。