患有乳糜泻HLA相关遗传风险的儿童中麦醇溶蛋白特异性免疫反应的发展

Development of gliadin-specific immune responses in children with HLA-associated genetic risk for celiac disease.

作者信息

Lammi Anne, Arikoski Pekka, Hakulinen Arja, Schwab Ursula, Uusitupa Matti, Heinonen Seppo, Savilahti Erkki, Kinnunen Tuure, Ilonen Jorma

机构信息

a 1 Department of Clinical Microbiology, University of Eastern Finland , Kuopio, Finland.

b 2 Department of Pediatrics, Kuopio University Hospital and University of Eastern Finland , Kuopio, Finland.

出版信息

Scand J Gastroenterol. 2016;51(2):168-77. doi: 10.3109/00365521.2015.1067328. Epub 2015 Jul 10.

Abstract

OBJECTIVE

The development of gliadin-specific antibody and T-cell responses were longitudinally monitored in young children with genetic risk for celiac disease (CD).

MATERIAL AND METHODS

291 newborn children positive for HLA-DQB102 and -DQA105 alleles were followed until 3-4 years of age by screening for tissue transglutaminase autoantibodies (tTGA) by using a commercial ELISA-based kit and antibodies to deamidated gliadin peptide (anti-DGP) by an immunofluorometric assay. Eighty-five of the children were also followed for peripheral blood gliadin-specific CD4(+) T-cell responses by using a carboxyfluorescein diacetate succinimidyl ester-based in vitro proliferation assay.

RESULTS

The cumulative incidence of tTGA seropositivity during the follow-up was 6.5%. CD was diagnosed in nine of the tTGA-positive children (3.1%) by duodenal biopsy at a median 3.5 years of age. All of the children with confirmed CD were both IgA and IgG anti-DGP positive at the time of tTGA seroconversion and in over half of the cases IgG anti-DGP positivity even preceded tTGA seroconversion. Peripheral blood T-cell responses to deamidated and native gliadin were detected in 40.5% and 22.2% of the children at the age of 9 months and these frequencies decreased during the follow-up to the levels of 22.2% and 8.9%, respectively.

CONCLUSIONS

Anti-DGP antibodies may precede tTGA seroconversion and thus frequent monitoring of both tTGA and anti-DGP antibodies may allow earlier detection of CD in genetically susceptible children. Peripheral blood gliadin-specific T-cell responses are relatively common in HLA-DQ2-positive children and are not directly associated with the development of CD.

摘要

目的

对具有乳糜泻(CD)遗传风险的幼儿,纵向监测麦醇溶蛋白特异性抗体和T细胞反应。

材料与方法

对291名HLA-DQB102和-DQA105等位基因阳性的新生儿进行随访,直至3 - 4岁,采用基于酶联免疫吸附测定(ELISA)的商用试剂盒筛查组织转谷氨酰胺酶自身抗体(tTGA),并通过免疫荧光测定法检测抗脱酰胺麦醇溶蛋白肽抗体(抗DGP)。其中85名儿童还通过基于羧基荧光素二乙酸琥珀酰亚胺酯的体外增殖试验,随访外周血麦醇溶蛋白特异性CD4(+) T细胞反应。

结果

随访期间tTGA血清阳性的累积发病率为6.5%。9名tTGA阳性儿童(3.1%)经十二指肠活检确诊为CD,中位年龄为3.5岁。所有确诊为CD的儿童在tTGA血清转化时IgA和IgG抗DGP均为阳性,超过半数的病例中IgG抗DGP阳性甚至先于tTGA血清转化。9个月大的儿童中,分别有40.5%和22.2%检测到外周血T细胞对脱酰胺和天然麦醇溶蛋白的反应,随访期间这些频率分别降至22.2%和8.9%。

结论

抗DGP抗体可能先于tTGA血清转化,因此频繁监测tTGA和抗DGP抗体可能有助于在遗传易感儿童中更早地检测出CD。外周血麦醇溶蛋白特异性T细胞反应在HLA-DQ2阳性儿童中相对常见,且与CD的发生无直接关联。

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