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BCG 挑战系统性红斑狼疮易感小鼠后获得部分长期临床改善。

Partial long-term clinical improvement after a BCG challenge in systemic lupus erythematosus-prone mice.

机构信息

Millennium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile.

出版信息

Autoimmunity. 2024 Dec;57(1):2380465. doi: 10.1080/08916934.2024.2380465. Epub 2024 Jul 21.

Abstract

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Fas mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.

摘要

系统性红斑狼疮 (SLE) 是一种自身免疫性疾病,导致免疫耐受的破坏。目前的治疗主要涉及一般免疫抑制,增加感染的风险。另一方面,卡介苗 (BCG) 近年来已被研究作为自身免疫性疾病的潜在治疗方法,促使正在进行研究。本研究旨在评估 BCG 疫苗接种对 SLE 早期和晚期临床表现的影响在小鼠疾病模型中。MRL/MPJ-Fas 小鼠用 BCG 免疫或用 PBS 作为对照进行治疗。在免疫后 27 天 (早期) 和 56 天 (晚期) 评估疾病的进展。监测临床参数和蛋白尿。采集血液样本用于测量抗核抗体 (ANA)、抗双链 DNA (抗-dsDNA),并通过 ELISA 测定细胞因子。通过流式细胞术和组织病理学分析从小鼠中采集的样本。我们观察到 BCG 治疗组的小鼠临床症状改善,疾病后期蛋白尿减少,TNF-α 减少。然而,BCG 并没有引起 ANA、抗-dsDNA、组织病理学评分或免疫细胞浸润的显著变化。BCG 在 SLE 小鼠模型中仅部分有益,需要进一步研究以确定该疫苗诱导的免疫力是否可以抵消狼疮的自身免疫反应。

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