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血浆干扰素-γ与新生血管性年龄相关性黄斑变性的治疗反应不佳有关。

Plasma Interferon-gamma is Associated with Poor Treatment Response in Neovascular Age-Related Macular Degeneration.

作者信息

Thomsen Alexander Kai, Steffensen Maria Abildgaard, Villarruel Hinnerskov Jenni Martinez, Nielsen Amalie Thomsen, Vorum Henrik, Honoré Bent, Nissen Mogens Holst, Sørensen Torben Lykke

机构信息

Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark.

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

出版信息

Aging Dis. 2025 Apr 9. doi: 10.14336/AD.2024.1585.

Abstract

Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly. Aging is the most important risk factor for AMD, and the aging immune system seems to be involved in pathogenesis. This study investigates the systemic aging immune profile in relation to AMD stage and treatment response. Treatment-naïve patients with neovascular AMD (nAMD), intermediate AMD and healthy controls were included in this prospective study. Participants were examined for systemic aging immune profiles and compared to AMD stage, as well as initial and one-year treatment response in nAMD patients. Flowcytometry was performed to determine T cell differentiation (naïve, central memory and effector memory) and expression of costimulatory markers (CD27, CD28, CD56). Cytokine assays were performed to measure the concentrations of plasma cytokines IFN-γ, IL-1β, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-27, TNF-α. Polymorphisms of CFH and ARMS2 genes were compared in nAMD patients. Patients with nAMD had significantly higher proportions of central and effector memory CD8+ T cells compared to controls (both P &;lt 0.036). nAMD patients had significantly elevated concentrations of IFN-γ, IL-1β, IL-2, and IL-10 (all P &;lt 0.05). nAMD patients with poor initial treatment response had a significantly higher concentration of plasma IFN-γ compared to good responders (P =0.026). Patients with nAMD had a more advanced systemic aging immune profile with higher levels of T cell differentiation and plasma cytokines compared to controls. Poor initial response had elevated levels of plasma IFN-γ compared to good responders in nAMD.

摘要

年龄相关性黄斑变性(AMD)是老年人视力损害和失明的主要原因。衰老是AMD最重要的危险因素,衰老的免疫系统似乎参与了其发病机制。本研究调查了与AMD阶段和治疗反应相关的全身衰老免疫特征。本前瞻性研究纳入了未经治疗的新生血管性AMD(nAMD)患者、中度AMD患者和健康对照者。对参与者进行全身衰老免疫特征检查,并与AMD阶段以及nAMD患者的初始和一年治疗反应进行比较。采用流式细胞术测定T细胞分化(初始、中枢记忆和效应记忆)以及共刺激标志物(CD27、CD28、CD56)的表达。进行细胞因子检测以测量血浆细胞因子IFN-γ、IL-1β、IL-2、IL-6、IL-10、IL-12、IL-17、IL-22、IL-27、TNF-α的浓度。比较了nAMD患者CFH和ARMS2基因的多态性。与对照组相比,nAMD患者中枢和效应记忆CD8+T细胞的比例显著更高(P均<0.036)。nAMD患者的IFN-γ、IL-1β、IL-2和IL-10浓度显著升高(P均<0.05)。初始治疗反应较差的nAMD患者血浆IFN-γ浓度显著高于反应良好者(P =0.026)。与对照组相比,nAMD患者具有更高级的全身衰老免疫特征,T细胞分化水平和血浆细胞因子水平更高。在nAMD中,初始反应较差者的血浆IFN-γ水平高于反应良好者。

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