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细菌相关事件与成人克罗恩病发病和复发患者的免疫应答。

Bacteria-related Events and the Immunological Response of Onset and Relapse Adult Crohn's Disease Patients.

机构信息

Department of Immunology, Biomedical Research Institute Sant Pau [IIB Sant Pau], Barcelona, Spain.

Department of Digestive Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

出版信息

J Crohns Colitis. 2019 Jan 1;13(1):92-99. doi: 10.1093/ecco-jcc/jjy138.

Abstract

BACKGROUND AND AIMS

Crohn's disease [CD] is a chronic, systemic inflammatory disease characterised by periods of remission and flare-ups. It has been associated with a disturbed gastrointestinal barrier function, an increase in the transport of luminal contents into the tissue, and lower immune tolerance.

METHODS

Peripheral blood samples were collected from healthy controls and 33 adult active flare-up CD patients. We classified patients as onset or relapse flare-up subjects, according to the days of disease evolution. Plasma levels of lipopolysaccharide-binding protein [LBP], fatty acid-binding proteins [FABP], and antibodies against bacterial lysates, interferons [IFN] and interleukin-6 [IL6] were measured by enzyme-linked immunosorbent assay [ELISA] in each group of patients.

RESULTS

Onset CD patients had higher plasma levels of LBP [57.32 ± 38.86 vs 30.22 ± 9.80 µg/ml] and IFNα [1.25 ± 0.23 vs 0.95 ± 0.36 log10pg/ml] and lower levels of immunoglobulins G and A [IgG and IgA] antibodies against bacterial lysates than relapse CD patients. We also observed a subgroup of onset patients with the highest levels of LBP. In this subgroup, LBP correlated negatively with C-reactive protein [CRP]. Onset and relapse CD patients had similar levels of FABP6 and FABP2, though LBP and FABP6 correlated positively only in relapse patients. In relapse patients, anti-E coli IgG antibodies correlated positively with systemic IL6 and IFNα levels.

CONCLUSIONS

Our findings suggest that onset and relapse flare-ups in adult CD patients are related to different systemic immune-related bacterial events. Characterising these differences may provide insights into the aetiology of Crohn's disease, and would help in the selection of appropriate therapies.

摘要

背景与目的

克罗恩病(CD)是一种慢性、全身性炎症性疾病,其特征为缓解期和发作期。它与胃肠道屏障功能紊乱、腔内内容物向组织内的转运增加以及免疫耐受降低有关。

方法

采集健康对照者和 33 例成人活动期 CD 患者的外周血样本。根据疾病进展天数,我们将患者分为初发或复发发作患者。采用酶联免疫吸附试验(ELISA)检测各组患者的血浆脂多糖结合蛋白(LBP)、脂肪酸结合蛋白(FABP)和针对细菌裂解物、干扰素(IFN)和白细胞介素-6(IL6)的抗体水平。

结果

初发 CD 患者的血浆 LBP [57.32 ± 38.86 比 30.22 ± 9.80 µg/ml]和 IFNα [1.25 ± 0.23 比 0.95 ± 0.36 log10pg/ml]水平较高,针对细菌裂解物的 IgG 和 IgA 抗体水平较低;与复发 CD 患者相比,我们还观察到一组初发患者的 LBP 水平最高。在这个亚组中,LBP 与 C 反应蛋白(CRP)呈负相关。初发和复发 CD 患者的 FABP6 和 FABP2 水平相似,但 LBP 仅与复发患者的 FABP6 呈正相关。在复发患者中,抗大肠杆菌 IgG 抗体与全身 IL6 和 IFNα 水平呈正相关。

结论

我们的研究结果表明,成人 CD 患者的初发和复发发作与不同的全身性免疫相关的细菌事件有关。这些差异的特征可能为克罗恩病的病因提供深入的了解,并有助于选择适当的治疗方法。

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