Oishi Saori, Tsukiji Nagaharu, Segawa Takahiro, Takano Katsuhiro, Hasuda Norio, Suzuki-Inoue Katsue
Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Japan.
Center for Life Science Research, University of Yamanashi, Japan.
Res Pract Thromb Haemost. 2023 Nov 23;8(1):102273. doi: 10.1016/j.rpth.2023.102273. eCollection 2024 Jan.
Gorham-Stout disease (GSD) is a form of lymphangiomatosis of unknown etiology, characterized by abnormal distribution of lymphatic vessels. Platelets and lymphangiogenesis are closely related via C-type lectin-like receptor 2 (CLEC-2)/podoplanin.
Despite similarities between abnormal lymphatic vessels in CLEC-2-deficient mice and patients with GSD, whether CLEC-2 on platelets is involved in GSD pathogenesis is unknown.
We examined CLEC-2 expression in platelets of a patient with lethal GSD. Most of the patient's platelets expressed aberrant CLEC-2 that was not detectable by certain monoclonal antibodies for human CLEC-2. Further, this population was not activated by a CLEC-2-activating snake venom, rhodocytin. Possible causes of abnormal CLEC-2 including anti-CLEC-2 autoantibodies, podoplanin binding to CLEC-2, and pathogenic gene alteration were excluded.
We believe that this is the first report of a patient with structurally and functionally abnormal CLEC-2. CLEC-2 abnormality may be associated with dysregulated lymphangiogenesis in GSD.
戈勒姆-斯托特病（GSD）是一种病因不明的淋巴管瘤病，其特征是淋巴管分布异常。血小板与淋巴管生成通过C型凝集素样受体2（CLEC-2）/血小板结合蛋白密切相关。
尽管CLEC-2缺陷小鼠的异常淋巴管与GSD患者的异常淋巴管存在相似之处，但尚不清楚血小板上的CLEC-2是否参与GSD的发病机制。
我们检测了一名致命性GSD患者血小板中CLEC-2的表达。该患者的大多数血小板表达异常的CLEC-2，某些针对人CLEC-2的单克隆抗体无法检测到这种异常表达。此外，该群体未被CLEC-2激活蛇毒红藻毒素激活。排除了异常CLEC-2的可能原因，包括抗CLEC-2自身抗体、血小板结合蛋白与CLEC-2的结合以及致病基因改变。
我们认为这是首例关于CLEC-2结构和功能异常患者的报告。CLEC-2异常可能与GSD中淋巴管生成失调有关。
