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与家族性地中海热相比,白塞病中的免疫和炎症基因表达有所不同。

Immune and inflammatory gene expressions are different in Behçet's disease compared to those in Familial Mediterranean Fever.

作者信息

Özdemir Filiz Türe, Demiralp Emel Ekşioğlu, Aydın Sibel Z, Atagündüz Pamir, Ergun Tülin, Direskeneli Haner

机构信息

Department of Immunology, Marmara University School of Medicine, İstanbul, Turkey.

Department of Immunology, Marmara University School of Medicine, İstanbul, Turkey; Department of Immunology, Memorial Şişli Hospital, İstanbul, Turkey.

出版信息

Eur J Rheumatol. 2016 Dec;3(4):146-152. doi: 10.5152/eurjrheum.2016.15099. Epub 2016 Dec 1.

Abstract

OBJECTIVE

The immune classification of Behçet's disease (BD) is still controversial. In this study, we aimed to compare the immune/inflammatory gene expressions in BD with those in familial Mediterranean fever (FMF), an autoinflammatory disorder with innate immune activation.

MATERIAL AND METHODS

CD4+ T cells and CD14+ monocytes were isolated from the peripheral blood mononuclear cells of Behçet's disease patients (n=10), FMF (n=6) patients, and healthy controls (n=4) with microbeads, and then, the mRNA was isolated. The expressions of 440 genes associated with immune and inflammatory responses were studied with a focused DNA microarray using a chemiluminescent tagging system. Changes above 1.5-fold and below 0.8-fold were accepted to be significant.

RESULTS

In BD patients, in the CD4+ T-lymphocyte subset, interleukin 18 receptor accessory protein (1.7-fold), IL-7 receptor (1.9-fold), and prokineticin 2 (2.5-fold) were all increased compared to those in FMF patients, whereas chemokine (C-X3-C motif ) receptor-1 (CX3CR1) (0.7-fold) and endothelial cell growth factor-1 (0.6-fold) were decreased. In the CD14+ monocyte population, the V-fos FBJ murine osteosarcoma viral oncogene homolog (1.5-fold), Interleukin-8 (IL-8) (2.1-fold), and Tumor Necrosis Factor alpha (TNF-α) (1.8-fold) were all increased, whereas the chemokine (C-C motif ) ligand 5 (CCL5) (0.6-fold), C-C chemokine receptor type 7 (0.6-fold), and CX3CR1 (0.7-fold) were decreased, again when compared to those in FMF. Compared to healthy controls in the CD4+ T-lymphocyte population, in both BD and FMF patients, pro-platelet basic protein and CD27 had elevated expression. In BD and FMF patients, 24 and 19 genes, respectively, were downregulated, with 15 overlapping genes between both disorders. In the CD14+ monocytes population, chemokine (C-C motif ) receptor-1 (CCR1) was upregulated both in BD and FMF patients compared to that in the controls, whereas CCL5 was downregulated.

CONCLUSION

Immune and inflammatory gene expressions seem to be variable in both the innate (CD14+) and adaptive (CD4+) immune responses in BD and FMF patients compared to those in controls, suggesting differences in immune regulation between the two disorders.

摘要

目的

白塞病(BD)的免疫分类仍存在争议。在本研究中,我们旨在比较BD与家族性地中海热(FMF,一种具有先天性免疫激活的自身炎症性疾病)患者的免疫/炎症基因表达情况。

材料与方法

使用微珠从白塞病患者(n = 10)、FMF患者(n = 6)和健康对照者(n = 4)的外周血单个核细胞中分离出CD4 + T细胞和CD14 + 单核细胞,然后提取mRNA。使用化学发光标记系统,通过聚焦DNA微阵列研究与免疫和炎症反应相关的440个基因的表达。变化超过1.5倍和低于0.8倍被认为具有显著性。

结果

在BD患者中,与FMF患者相比,CD4 + T淋巴细胞亚群中的白细胞介素18受体辅助蛋白(1.7倍)、IL - 7受体(1.9倍)和促动力蛋白2(2.5倍)均升高,而趋化因子(C - X3 - C基序)受体 - 1(CX3CR1)(0.7倍)和内皮细胞生长因子 - 1(0.6倍)降低。在CD14 + 单核细胞群体中,V - fos FBJ小鼠骨肉瘤病毒癌基因同源物(1.5倍)、白细胞介素 - 8(IL - 8)(2.1倍)和肿瘤坏死因子α(TNF - α)(1.8倍)均升高,而趋化因子(C - C基序)配体5(CCL5)(0.6倍)、C - C趋化因子受体7型(0.6倍)和CX3CR1(0.7倍)降低,同样是与FMF患者相比。与健康对照者的CD4 + T淋巴细胞群体相比,BD和FMF患者的前血小板碱性蛋白和CD27表达均升高。在BD和FMF患者中,分别有24个和19个基因下调,两种疾病之间有15个重叠基因。在CD14 + 单核细胞群体中,与对照相比,BD和FMF患者的趋化因子(C - C基序)受体 - 1(CCR1)均上调,而CCL5下调。

结论

与对照相比,BD和FMF患者在先天性(CD14 +)和适应性(CD4 +)免疫反应中的免疫和炎症基因表达似乎存在差异,提示这两种疾病在免疫调节方面存在差异。

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