Abstract：
BACKGROUND: Galectin-9 (Gal-9) has been implicated in allergic and autoimmune diseases, but its role and relevance in chronic spontaneous urticaria (CSU) are unclear.
OBJECTIVE: To characterize the role and relevance of Gal-9 in the pathogenesis of CSU.
METHODS: We assessed 60 CSU patients for their expression of Gal-9 on circulating eosinophils and basophils as well as T cell expression of the Gal-9 receptor TIM-3, compared them with 26 healthy controls (HCs), and explored possible links with disease features including disease activity (urticaria activity score, UAS), total IgE, basophil activation test (BAT), and response to omalizumab treatment. We also investigated potential drivers of Gal-9 expression by eosinophils and basophils.
RESULTS: Our CSU patients had markedly increased rates of circulating Gal-9+ eosinophils and basophils and high numbers of lesional Gal-9+ cells. High rates of blood Gal-9+ eosinophils/basophils were linked to high disease activity, IgE levels, and BAT negativity. Serum levels of TNF-α were positively correlated with circulating Gal-9+ eosinophils/basophils, and TNF-α markedly upregulated Gal-9 on eosinophils. CSU patients who responded to omalizumab treatment had more Gal-9+ eosinophils/basophils than non-responders, and omalizumab reduced blood levels of Gal-9+ eosinophils/basophils in responders. Gal-9+ eosinophils/basophils were negatively correlated with TIM-3+TH17 cells.
CONCLUSIONS: Our findings demonstrate a previously unrecognized involvement of the Gal-9/TIM-3 pathway in the pathogenesis CSU and call for studies that explore its relevance.
OBJECTIVE: To characterize the role and relevance of Gal-9 in the pathogenesis of CSU.
METHODS: We assessed 60 CSU patients for their expression of Gal-9 on circulating eosinophils and basophils as well as T cell expression of the Gal-9 receptor TIM-3, compared them with 26 healthy controls (HCs), and explored possible links with disease features including disease activity (urticaria activity score, UAS), total IgE, basophil activation test (BAT), and response to omalizumab treatment. We also investigated potential drivers of Gal-9 expression by eosinophils and basophils.
RESULTS: Our CSU patients had markedly increased rates of circulating Gal-9+ eosinophils and basophils and high numbers of lesional Gal-9+ cells. High rates of blood Gal-9+ eosinophils/basophils were linked to high disease activity, IgE levels, and BAT negativity. Serum levels of TNF-α were positively correlated with circulating Gal-9+ eosinophils/basophils, and TNF-α markedly upregulated Gal-9 on eosinophils. CSU patients who responded to omalizumab treatment had more Gal-9+ eosinophils/basophils than non-responders, and omalizumab reduced blood levels of Gal-9+ eosinophils/basophils in responders. Gal-9+ eosinophils/basophils were negatively correlated with TIM-3+TH17 cells.
CONCLUSIONS: Our findings demonstrate a previously unrecognized involvement of the Gal-9/TIM-3 pathway in the pathogenesis CSU and call for studies that explore its relevance.
摘要：
背景：半乳糖凝集素-9（Gal-9）与过敏性和自身免疫性疾病有关，但其在慢性自发性荨麻疹（CSU）中的作用和相关性尚不清楚。
目的：探讨Gal-9在CSU发病机制中的作用和相关性。
方法：我们评估了60例CSU患者在循环嗜酸性粒细胞和嗜碱性粒细胞上Gal-9的表达以及Gal-9受体TIM-3的T细胞表达，并将其与26例健康对照（HCs）进行比较。并探讨了与疾病特征的可能联系，包括疾病活动(荨麻疹活动评分，UAS),总IgE,嗜碱性粒细胞活化试验(BAT),和对奥马珠单抗治疗的反应。我们还研究了嗜酸性粒细胞和嗜碱性粒细胞表达Gal-9的潜在驱动因素。
结果：我们的CSU患者循环Gal-9+嗜酸性粒细胞和嗜碱性粒细胞的比率明显升高，病变Gal-9+细胞的数量也很高。高比例的血液Gal-9+嗜酸性粒细胞/嗜碱性粒细胞与高疾病活动有关,IgE水平,和BAT消极。血清TNF-α水平与循环Gal-9+嗜酸性粒细胞/嗜碱性粒细胞呈正相关,TNF-α明显上调嗜酸性粒细胞Gal-9。对奥马珠单抗治疗有反应的CSU患者比无反应者有更多的Gal-9+嗜酸性粒细胞/嗜碱性粒细胞，和奥马珠单抗降低了应答者的Gal-9+嗜酸性粒细胞/嗜碱性粒细胞的血液水平。Gal-9+嗜酸性粒细胞/嗜碱性粒细胞与TIM-3+TH17细胞呈负相关。
结论：我们的研究结果表明Gal-9/TIM-3通路在CSU发病机制中的参与以前未被认识到，因此需要研究探讨其相关性。
目的：探讨Gal-9在CSU发病机制中的作用和相关性。
方法：我们评估了60例CSU患者在循环嗜酸性粒细胞和嗜碱性粒细胞上Gal-9的表达以及Gal-9受体TIM-3的T细胞表达，并将其与26例健康对照（HCs）进行比较。并探讨了与疾病特征的可能联系，包括疾病活动(荨麻疹活动评分，UAS),总IgE,嗜碱性粒细胞活化试验(BAT),和对奥马珠单抗治疗的反应。我们还研究了嗜酸性粒细胞和嗜碱性粒细胞表达Gal-9的潜在驱动因素。
结果：我们的CSU患者循环Gal-9+嗜酸性粒细胞和嗜碱性粒细胞的比率明显升高，病变Gal-9+细胞的数量也很高。高比例的血液Gal-9+嗜酸性粒细胞/嗜碱性粒细胞与高疾病活动有关,IgE水平,和BAT消极。血清TNF-α水平与循环Gal-9+嗜酸性粒细胞/嗜碱性粒细胞呈正相关,TNF-α明显上调嗜酸性粒细胞Gal-9。对奥马珠单抗治疗有反应的CSU患者比无反应者有更多的Gal-9+嗜酸性粒细胞/嗜碱性粒细胞，和奥马珠单抗降低了应答者的Gal-9+嗜酸性粒细胞/嗜碱性粒细胞的血液水平。Gal-9+嗜酸性粒细胞/嗜碱性粒细胞与TIM-3+TH17细胞呈负相关。
结论：我们的研究结果表明Gal-9/TIM-3通路在CSU发病机制中的参与以前未被认识到，因此需要研究探讨其相关性。
