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HLA单倍型、白细胞介素8水平及弓形虫感染在确定乳糜泻表型中的作用

Contributions of HLA haplotypes, IL8 level and Toxoplasma gondii infection in defining celiac disease's phenotypes.

作者信息

Rostami-Nejad Mohammad, Hejazi Seyed Hossein, Peña Amado Salvador, Asadzadeh-Aghdaei Hamid, Rostami Kamran, Volta Umberto, Zali Mohammad Reza

机构信息

Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical sciences, Isfahan, Iran.

出版信息

BMC Gastroenterol. 2018 May 18;18(1):66. doi: 10.1186/s12876-018-0796-9.

DOI:10.1186/s12876-018-0796-9
PMID:29776388
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5960085/
Abstract

BACKGROUND

It is not clear why some patients with coeliac disease (CD) present with severe symptoms and small intestinal mucosal damages while others present with milder symptoms and no frank enteropathy. There is no study to assess the associated factors with mild/severe symptoms and enteropathy. The terminologies like latent, silent and potential are difficult to use and are unrepresentative. In the present study we describe coeliac disease's phenotypes based on HLA haplotypes, IL8 production and past infection with Toxoplasma gondii (T. gondii) infection.

METHODS

In this case-control study, sera originating from 150 healthy subjects and 150 patients diagnosed with CD during the years 2013-14 were analyzed for the presence of antibodies specific T. gondii of the IgG and IgM subclasses. The level of IL8 were measured and HLA-DQ2 and HLA-DQ8 alleles were genotyped. The correlation between these parameters and the damages in intestinal mucosal were assessed using an accepted histopathological classification.

RESULTS

High levels of IgG antibodies against T. gondii were found in the sera of control group compared to the CD group (52.6% vs. 39.4%, P = 0.02). Mean serum levels of IL8 was significantly higher in CD patients compared with control (P ≤ 0.05). By comparing the level of anti- T. gondii IgG and mucosal damage in celiac disease, we found a significant relationship between the severity of mucosal damages and anti- T. gondii IgG level (P = 0.02). No correlation was detected between Toxoplasma gondii infection and types of HLA (P > 0.05). However, patients with severely abnormal histology carried HLA-DQ2 risk alleles (92 patients (61%)) more often than the controls and those with mild histological abnormalities.

CONCLUSIONS

CD patients with severe histological changes had more often Toxoplasma gondii infection than those affected with mild histological features. This suggests that CD's phenotypes are correlated to additional factors like infections and to particular HLA DQ2 alleles that may need additional investigations and potentially will require additional treatment.

摘要

背景

目前尚不清楚为什么一些乳糜泻(CD)患者会出现严重症状和小肠黏膜损伤,而另一些患者症状较轻且无明显肠病。尚无研究评估与轻度/重度症状及肠病相关的因素。“潜伏性”“无症状性”和“潜在性”等术语难以使用且不具代表性。在本研究中,我们基于HLA单倍型、白细胞介素8(IL8)产生以及既往弓形虫(T. gondii)感染情况来描述乳糜泻的表型。

方法

在这项病例对照研究中,分析了2013 - 2014年间来自150名健康受试者和150名被诊断为CD患者的血清中IgG和IgM亚类特异性弓形虫抗体的存在情况。检测了IL8水平并对HLA - DQ2和HLA - DQ8等位基因进行基因分型。使用公认的组织病理学分类评估这些参数与肠黏膜损伤之间的相关性。

结果

与CD组相比,对照组血清中抗弓形虫IgG抗体水平较高(52.6%对39.4%,P = 0.02)。CD患者的血清IL8平均水平显著高于对照组(P≤0.05)。通过比较乳糜泻患者抗弓形虫IgG水平与黏膜损伤情况,我们发现黏膜损伤严重程度与抗弓形虫IgG水平之间存在显著相关性(P = 0.02)。未检测到弓形虫感染与HLA类型之间的相关性(P>0.05)。然而,组织学严重异常的患者携带HLA - DQ2风险等位基因(92例患者(61%))的频率高于对照组以及组织学轻度异常的患者。

结论

组织学变化严重的CD患者比组织学特征较轻的患者更常感染弓形虫。这表明CD的表型与感染等其他因素以及特定的HLA DQ2等位基因相关,可能需要进一步研究,并且可能需要额外的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51b8/5960085/9fa63d4cd628/12876_2018_796_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51b8/5960085/9fa63d4cd628/12876_2018_796_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51b8/5960085/9fa63d4cd628/12876_2018_796_Fig2_HTML.jpg

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