Montén C, Torinsson Naluai Å, Agardh D
Department of Clinical Sciences, Diabetes and Celiac Disease Unit, Lund University, Malmö, Sweden.
Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Clin Exp Immunol. 2016 Dec;186(3):387-392. doi: 10.1111/cei.12864. Epub 2016 Oct 7.
Neurotensin (NT) is a gut hormone functioning proinflammatory through nuclear factor kappa B (NF-κB) and interleukin (IL)-8 secretion or anti-inflammatory through epidermal growth factor receptors. NT mRNA is down-regulated in duodenal biopsies of children with untreated coeliac disease. The aim of this study was to investigate if plasma pro-NT levels correlated with the degree of intestinal mucosal damage and tissue transglutaminase autoantibody (tTGA) levels in children with coeliac disease. Fasting plasma samples from 96 children with coeliac disease and 89 non-coeliac disease controls were analysed for NT precursor fragment pro-NT 1-117 by a chemiluminometric immunoassay. Pro-NT levels were compared with NT mRNA from duodenal biopsies, assessed previously with quantitative polymerase chain reaction (PCR). Illumina core exome arrays were used for human leucocyte antigen (HLA) typing and the Marsh criteria applied to score mucosal damage. Tissue TGA was measured by radio binding assay. A general linear model compared pro-NT levels with diagnosis of coeliac disease, Marsh score and HLA DQ haplotype. Spearman's rank test was used to compare pro-NT levels with tTGA, age and duodenal NT mRNA levels, respectively. Plasma pro-NT levels were elevated in children with coeliac disease (median 23 pmol/l higher, P = 0·003) and in those with severe intestinal mucosal damage (median 24 pmol/l higher for ≥ Marsh 3b versus not, P = 0·0004). Pro-NT levels correlated further with tTGA (r = 0·22, P = 0·002), but not with duodenal NTS mRNA levels (r = -0·12, P = 0·14). Pro-NT was not associated with any of the HLA risk-haplotypes. Elevated peripheral pro-NT levels reflect more severe forms of active coeliac disease, indicating a potential role of NT in intestinal inflammation.
神经降压素（NT）是一种肠道激素，通过核因子κB（NF-κB）和白细胞介素（IL）-8分泌发挥促炎作用，或通过表皮生长因子受体发挥抗炎作用。在未经治疗的乳糜泻患儿的十二指肠活检中，NT mRNA表达下调。本研究旨在调查乳糜泻患儿血浆前NT水平是否与肠道黏膜损伤程度及组织转谷氨酰胺酶自身抗体（tTGA）水平相关。采用化学发光免疫分析法对96例乳糜泻患儿和89例非乳糜泻对照儿童的空腹血浆样本进行NT前体片段pro-NT 1-117分析。将前NT水平与十二指肠活检中的NT mRNA进行比较，此前已通过定量聚合酶链反应（PCR）对其进行评估。使用Illumina核心外显子阵列进行人类白细胞抗原（HLA）分型，并应用马什标准对黏膜损伤进行评分。通过放射结合试验测量组织TGA。采用一般线性模型比较前NT水平与乳糜泻诊断、马什评分和HLA DQ单倍型。分别使用Spearman秩和检验比较前NT水平与tTGA、年龄及十二指肠NT mRNA水平。乳糜泻患儿（中位数高23 pmol/l，P = 0.003）及肠道黏膜损伤严重的患儿（马什3b级及以上者中位数高24 pmol/l，P = 0.0004）血浆前NT水平升高。前NT水平与tTGA进一步相关（r = 0.22，P = 0.002），但与十二指肠NTS mRNA水平无关（r = -0.12，P = 0.14）。前NT与任何HLA风险单倍型均无关联。外周前NT水平升高反映了更严重形式的活动性乳糜泻，表明NT在肠道炎症中可能发挥作用。
