血浆干扰素-γ浓度:系统性慢性活动性EB病毒感染疾病活动性的潜在生物标志物

IF 2 Q4 VIROLOGY Frontiers in virology Pub Date : 2022-09-29 DOI:10.3389/fviro.2022.999929
Yukina Uemura, Ayaka Ohashi, M. Yoshimori, Miwako Nishio, T. Hirakawa, N. Shimizu, Naomi Wada, K. Imadome, A. Arai
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引用次数: 1

摘要

系统性慢性活动性EB病毒感染(sCAEBV)是一种棘手的疾病,表现为活化的EB病毒感染的T或NK细胞及其克隆增殖。当炎症症状持续并进行时,会出现噬血细胞性淋巴组织细胞增多症(HLH)的致命并发症,但迄今为止,其代表病理生理学的生物标志物和有效的治疗剂尚未开发出来。已知HLH患者外周血中干扰素-γ(IFN-γ)水平的升高与疾病状况有关,并且拮抗性抗IFN-γ抗体对HLH有效。我们检测了血浆IFN-γ水平,以研究其在sCAEBV疾病中的作用。sCAEBV是根据符合2017年发布的世界卫生组织分类中sCAEBV定义的标准诊断的。正如之前报道的那样,疾病活动性被定义为以下任何一种情况呈阳性:发烧、肝功能障碍、进行性皮肤病变、血管炎和葡萄膜炎。18名sCAEBV患者接受了检查。其血浆IFN-γ水平显著高于健康供体。有疾病活动的sCAEBV患者的水平高于无疾病活动的患者。在所有患者的EBV感染细胞中检测IFNG的mRNA表达。我们还检测到血浆IFN-γ水平与外周血单个核细胞中EBV感染细胞的mRNA水平之间的相关性。这些结果表明EBV感染的细胞在sCAEBV中产生IFN-γ。尽管差异不显著,但诊断时血浆IFN-γ水平高于40pg/mL的患者往往比水平较低的患者生存率较差。我们得出结论,血浆IFN-γ是一种潜在的生物标志物,表明sCAEBV的疾病活性。进一步研究将证实其重要性。
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Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infection
Systemic chronic active Epstein-Barr virus infection (sCAEBV) is an intractable disease that present activated EBV-infected T- or NK-cells and their clonal proliferation. When inflammatory symptoms persist and proceed, a lethal complication of hemophagocytic lymphohistiocytosis (HLH) develops, but its biomarker to represent the pathophysiology and an effective agent to cure have not been developed as of today. It is known that interferon-γ (IFN-γ) level in the peripheral blood increases in HLH correlatedly with the disease condition and that antagonistic anti-IFN-γ antibody is effective against HLH. We examined the plasma level of IFN-γ to investigate its role in the disease condition of sCAEBV. sCAEBV was diagnosed based on the criteria conforming to the definition of sCAEBV in the WHO classification issued in 2017. As it was previously reported, disease activity was defined as the condition positive for any one of the followings: fever, liver dysfunction, progressive skin lesions, vasculitis, and uveitis. Eighteen sCAEBV patients were examined. Their plasma IFN-γ levels were significantly higher than those of healthy donors. The levels in sCAEBV patients with disease activity were higher than those without disease activity. The mRNA expression of IFNG was detected in EBV-infected cells of all patients. We also detected a correlation between plasma IFN-γ levels and mRNA levels of EBV-infected cells in peripheral blood mononuclear cells. These results suggest that EBV-infected cells produce IFN-γ in sCAEBV. Although the difference was not significant, the patients whose plasma IFN-γ levels at diagnosis were higher than 40 pg/mL tended to result in poorer survival than those with lower levels. We concluded that plasma IFN-γ is a potential biomarker that indicates disease activity of sCAEBV. Further study shall confirm its significance.
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