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转谷氨酰胺酶抗体与 1 型糖尿病患儿及其家庭成员的乳糜泻

Transglutaminase antibodies and celiac disease in children with type 1 diabetes and in their family members.

机构信息

Scientific Laboratory, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Folkhälsan Research Center, Helsinki, Finland.

出版信息

Pediatr Diabetes. 2018 Mar;19(2):305-313. doi: 10.1111/pedi.12563. Epub 2017 Jul 26.

Abstract

OBJECTIVES

We set out to determine the prevalence of tissue transglutaminase antibodies (anti-tTG) and celiac disease (CD) in children with newly diagnosed type 1 diabetes (T1D) and their first-degree relatives (FDR). The hypothesis was that the individuals with both diabetes and CD form a distinct subgroup in terms of human leukocyte antigen (HLA) class II genetics, islet autoantibodies, and clinical characteristics at diabetes diagnosis.

SUBJECTS AND METHODS

This population-based observational study included 745 index children with T1D and their 2692 FDR from the Finnish Pediatric Diabetes Register. CD was ascertained by registers, patient records, and screening anti-tTG positive individuals for further testing.

RESULTS

Among the index children, 4.8% had anti-tTG at diabetes diagnosis, and at the end of the study 3.2% had CD. Among the relatives, 2.9% had anti-tTG (4.8% mothers, 2.4% fathers, and 2.1% siblings), and 2.5% had CD (4.6% mothers, 2.1% fathers, and 1.4% siblings). Anti-tTG and CD associated with the HLA DR3-DQ2 haplotype. The usual female predominance of CD patients was observed in relatives (70%) but not among index children (46%). The index children with both diseases had a lower number of detectable islet autoantibodies than those with diabetes alone.

CONCLUSIONS

The children with double diagnosis differed from those with diabetes alone in HLA genetics, humoral islet autoimmunity directed against fewer antigens, and in the lack of usual female preponderance among CD patients. Compared with 61% of the anti-tTG positive relatives, only 36% of anti-tTG positive index children developed CD implicating transient anti-tTG positivity at diagnosis of T1D.

摘要

目的

我们旨在确定新诊断为 1 型糖尿病(T1D)的儿童及其一级亲属(FDR)中组织转谷氨酰胺酶抗体(抗 tTG)和乳糜泻(CD)的患病率。假设是,同时患有糖尿病和 CD 的个体在人类白细胞抗原(HLA)II 类遗传学、胰岛自身抗体和糖尿病诊断时的临床特征方面形成一个独特的亚组。

材料和方法

本基于人群的观察性研究纳入了来自芬兰儿科糖尿病登记处的 745 名 T1D 指数儿童及其 2692 名 FDR。通过登记、病历和筛查抗 tTG 阳性个体进行进一步检测来确定 CD。

结果

在指数儿童中,4.8%在糖尿病诊断时具有抗 tTG,在研究结束时,3.2%患有 CD。在亲属中,2.9%具有抗 tTG(4.8%母亲、2.4%父亲和 2.1%兄弟姐妹),2.5%患有 CD(4.6%母亲、2.1%父亲和 1.4%兄弟姐妹)。抗 tTG 和 CD 与 HLA DR3-DQ2 单倍型相关。在亲属中观察到 CD 患者通常以女性为主(70%),但在指数儿童中则不然(46%)。患有两种疾病的指数儿童的可检测胰岛自身抗体数量少于仅患有糖尿病的儿童。

结论

与单独患有糖尿病的儿童相比,患有双重诊断的儿童在 HLA 遗传学、针对较少抗原的体液胰岛自身免疫以及 CD 患者中缺乏通常的女性优势方面存在差异。与 61%的抗 tTG 阳性亲属相比,仅 36%的抗 tTG 阳性指数儿童发展为 CD,这意味着在 T1D 诊断时存在短暂的抗 tTG 阳性。

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