Droege Freya, Pylaeva Ekaterina, Siakaeva Elena, Bordbari Sharareh, Spyra Ilona, Thangavelu Kruthika, Lueb Carolin, Domnich Maksim, Lang Stephan, Geisthoff Urban, Jablonska Jadwiga
Department of Otorhinolaryngology, Head and Neck Surgery, Essen University Hospital, University Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany.
Translational Oncology, Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany.
J Clin Med. 2020 Mar 12;9(3):767. doi: 10.3390/jcm9030767.
Hereditary hemorrhagic telangiectasia (HHT) is characterized by mucocutaneous telangiectases and visceral vascular malformations. Individuals suffering from HHT have a significantly increased risk of bacterial infections, but the mechanisms involved in this are not clear. White blood cell subpopulations were estimated with flow cytometry in 79 patients with HHT and 45 healthy individuals, and association with clinicopathological status was assessed. A prominent decrease in absolute numbers of T cells in HHT was revealed (0.7 (0.5-1.1) vs. 1.3 (0.8-1.6), 10/mL, < 0.05), and in multivariate regression analysis, hemoglobin level was associated with lymphopenia (OR = 0.625, 95% CI: 0.417-0.937, < 0.05). Although no changes in absolute numbers of neutrophils and monocytes were observed, we revealed a significant impairment of neutrophil antibacterial functions in HHT ( = 9), compared to healthy individuals ( = 7), in vitro. The release of neutrophil extracellular traps (NETs) against MOI10 was significantly suppressed in HHT (mean area per cell, mm: 76 (70-92) vs. 121 (97-128), < 0.05), due to impaired filamentous actin organization (% of positive cells: 69 (59-77) vs. 92 (88-94), < 0.05). To conclude, this study reveals the categories of patients with HHT that are prone to immunosuppression and require careful monitoring, and suggests a potential therapeutic strategy based on the functional activation of neutrophils.
遗传性出血性毛细血管扩张症（HHT）的特征为黏膜皮肤毛细血管扩张和内脏血管畸形。HHT患者发生细菌感染的风险显著增加，但其相关机制尚不清楚。我们采用流式细胞术对79例HHT患者和45名健康个体的白细胞亚群进行了评估，并分析了其与临床病理状态的相关性。结果显示，HHT患者的T细胞绝对数量显著减少（0.7（0.5 - 1.1）对1.3（0.8 - 1.6），×10⁹/mL，P < 0.05），多因素回归分析表明，血红蛋白水平与淋巴细胞减少相关（OR = 0.625，95%CI：0.417 - 0.937，P < 0.05）。虽然未观察到中性粒细胞和单核细胞绝对数量的变化，但与健康个体（n = 7）相比，我们发现HHT患者（n = 9）的中性粒细胞抗菌功能存在显著损害。在体外，HHT患者针对MOI 10的中性粒细胞胞外陷阱（NETs）释放显著受到抑制（每个细胞的平均面积，mm²：76（70 - 92）对121（97 - 128），P < 0.05），这是由于丝状肌动蛋白组织受损（阳性细胞百分比：69（59 - 77）对92（88 - 94），P < 0.05）。总之，本研究揭示了HHT患者中易于发生免疫抑制且需要密切监测的类别，并提出了基于中性粒细胞功能激活的潜在治疗策略。
