共济失调毛细血管扩张症 (AT) 是一种罕见的常染色体隐性遗传疾病，其特征是严重的神经变性、联合免疫缺陷和恶性疾病风险增加。 AT 的治疗选择有限，并且患者的长期生存预后仍然严峻，这主要是由于慢性呼吸道疾病、恶性肿瘤和神经系统并发症的出现。了解 AT 中免疫系统的失调对于开发新的治疗策略至关重要。在这种情况下，我们对一组 AT 患者 (n = 65) 的淋巴细胞亚群分布进行了回顾性纵向免疫监测。此外，我们对 12 名 AT 患者亚组的外周血单核细胞进行了 FACS 分析，以检查 NK 和 T 细胞的激活和功能标记物的表达。我们观察到外周血 CD3 CD8 细胞毒性 T 细胞、CD3 CD4 T 辅助细胞和 CD19 B 细胞的水平降低，而 CD3-CD56 NK 细胞和 CD3 CD56 NKT 样细胞的数量与年龄匹配的对照相似。值得注意的是，T、B 或 NK 细胞计数的年龄依赖性动力学与 AT 患者恶性肿瘤的发生之间没有关联。此外，我们的结果表明，AT 中 NK 细胞和 T 细胞对细胞因子刺激的反应发生改变，NK 细胞中 TRAIL、FasL 和 CD16 表达水平增加，并且 AT 中 T 细胞激活水平升高，表达量显着升高IFN-γ、CD107a、TRAIL 和 FasL 的水平。总之，这些发现意味着 AT 淋巴细胞，特别是 T 细胞和 NK 细胞的功能改变，揭示了创新疗法的潜在途径。版权所有 © 2024 Graafen, Heinze, Albinger, Salzmann-Manrique, Ganß, Hünecke, Cappel, Wölke, Donath,特里施勒、泰伦、海勒、柯尼希斯、埃尔、巴德尔、克林盖贝尔、克鲁斯曼、齐伦、舒伯特和乌尔里希。

Ataxia telangiectasia (AT) is a rare autosomal-recessive disorder characterized by profound neurodegeneration, combined immunodeficiency, and an increased risk for malignant diseases. Treatment options for AT are limited, and the long-term survival prognosis for patients remains grim, primarily due to the emergence of chronic respiratory pathologies, malignancies, and neurological complications. Understanding the dysregulation of the immune system in AT is fundamental for the development of novel treatment strategies. In this context, we performed a retrospective longitudinal immunemonitoring of lymphocyte subset distribution in a cohort of AT patients (n = 65). Furthermore, we performed FACS analyses of peripheral blood mononuclear cells from a subgroup of 12 AT patients to examine NK and T cells for the expression of activating and functional markers. We observed reduced levels of peripheral blood CD3+CD8+ cytotoxic T cells, CD3+CD4+ T helper cells, and CD19+ B cells, whereas the amount of CD3--CD56+ NK cells and CD3+CD56+ NKT-like cells was similar compared with age-matched controls. Notably, there was no association between the age-dependent kinetic of T-, B-, or NK-cell counts and the occurrence of malignancy in AT patients. Additionally, our results indicate an altered NK- and T-cell response to cytokine stimulation in AT with increased levels of TRAIL, FasL, and CD16 expression in NK cells, as well as an elevated activation level of T cells in AT with notably higher expression levels of IFN-γ, CD107a, TRAIL, and FasL. Together, these findings imply function alterations in AT lymphocytes, specifically in T and NK cells, shedding light on potential pathways for innovative therapies.Copyright © 2024 Graafen, Heinze, Albinger, Salzmann-Manrique, Ganß, Hünecke, Cappel, Wölke, Donath, Trischler, Theilen, Heller, Königs, Ehl, Bader, Klingebiel, Klusmann, Zielen, Schubert and Ullrich.