Human interferon regulatory factor 5 homologous epitopes of Epstein-Barr virus and Mycobacterium avium subsp paratuberculosis induce a specific humoral and cellular immune response in multiple sclerosis patients

Human interferon regulatory factor 5 homologous epitopes of Epstein-Barr virus and Mycobacterium avium subsp paratuberculosis induce a specific humoral and cellular immune response in multiple sclerosis patients
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DOI:
10.1177/1352458514557304
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发表时间:
2015-07-01
影响因子:
5.8
通讯作者:
Sechi, Leonardo Antonio
Sechi, Leonardo Antonio
中科院分区:
医学2区
文献类型:
--
作者:
Cossu, Davide;Mameli, Giuseppe;Sechi, Leonardo Antonio

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背景:大量报告表明 Epstein-Barr 病毒 (EBV) 和鸟分枝杆菌亚种之间存在关联。目的:为了更好地了解这两种病原体的作用,我们研究了选定的抗原肽诱导的宿主反应。方法:我们在几名 MS 患者和结果:与 HC 相比,针对这些肽的抗体在 MS 患者中非常普遍。对于MS患者,BOLF1(305-320)、MAP_4027(18-32)和IRF5(424-434)肽能够主要诱导Th1相关细胞因子的分泌,而Th2相关细胞因子则下调。对部分 MS 患者进行的流式细胞术分析强调,这些肽能够诱导促炎细胞因子的释放:CD4(+) 和 CD8(+) T 淋巴细胞释放 IFN- 和 TNF-,CD14(+) 单核细胞释放 IL-6 和 TNF-。 结论:我们的数据表明,与 HC 相比,EBV 和 MAP 表位在 MS 患者中引起一致的体液反应,并且上述肽能够诱导与 MS 相关的 T 细胞介导的反应。
Background: A large number of reports indicate the association of Epstein-Barr virus (EBV), and Mycobacterium avium subsp. paratuberculosis (MAP) with multiple sclerosis (MS).Objective: To gain a better understanding of the role of these two pathogens, we investigated the host response induced by selected antigenic peptides.Methods: We examined both humoral and cell-mediated responses against peptides deriving from EBV tegument protein BOLF1, the MAP_4027 and the human interferon regulatory factor 5 (IRF5(424-434)) homolog in several MS patients and healthy controls (HCs).Results: Antibodies against these peptides were highly prevalent in MS patients compared to HCs. Concerning MS patients, BOLF1(305-320), MAP_4027(18-32) and IRF5(424-434) peptides were able to induce mainly Th1-related cytokines secretion, whereas Th2-related cytokines were down-regulated. Flow cytometry analyses performed on a subset of MS patients highlighted that these peptides were capable of inducing the release of pro-inflammatory cytokines: IFN- and TNF- by CD4(+) and CD8(+) T lymphocytes, and IL-6 and TNF- by CD14(+) monocyte cells.Conclusion: Our data demonstrated that both EBV and MAP epitopes elicit a consistent humoral response in MS patients compared to HCs, and that the aforementioned peptides are able to induce a T-cell-mediated response that is MS correlated.