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血小板去唾液酸化与循环滤泡辅助性 T 细胞在血小板减少症患者中的相关性。

Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia.

机构信息

Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, China.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States.

出版信息

Front Immunol. 2022 Apr 1;13:810620. doi: 10.3389/fimmu.2022.810620. eCollection 2022.

Abstract

Thrombocytopenia is a multifactorial condition that frequently involves concomitant defects in platelet production and clearance. The physiopathology of low platelet count in thrombocytopenia remains unclear. Sialylation on platelet membrane glycoprotein and follicular helper T cells (TFHs) are thought to be the novel platelet clearance pathways. The aim of this study was to clarify the roles of platelet desialylation and circulating TFHs in patients with immune thrombocytopenia (ITP) and non-ITP thrombocytopenia. We enrolled 190 patients with ITP and 94 patients with non-ITP related thrombocytopenia including case of aplastic anemia (AA) and myelodysplastic syndromes (MDS). One hundred and ten healthy volunteers were included as controls. We found significantly increased desialylated platelets in patients with ITP or thrombocytopenia in the context of AA and MDS. Platelet desialylation was negatively correlated with platelet count. Meanwhile, the circulating TFH levels in patients with thrombocytopenia were significantly higher than those of normal controls, and were positively correlated with desialylated platelet levels. Moreover, TFHs-related chemokine CXCL13 and apoptotic platelet levels were abnormally high in ITP patients. The upregulation of pro-apoptotic proteins and the activation of the MAPK/mTOR pathway were observed in the same cohort. These findings suggested that platelet desialylation and circulating TFHs may become the potential biomarkers for evaluating the disease process associated with thrombocytopenia in patients with ITP and non-ITP.

摘要

血小板减少症是一种多因素疾病,常伴有血小板生成和清除的同时缺陷。血小板减少症中血小板计数降低的病理生理学仍不清楚。血小板膜糖蛋白的唾液酸化和滤泡辅助 T 细胞(TFHs)被认为是新的血小板清除途径。本研究旨在阐明血小板去唾液酸化和循环 TFHs 在免疫性血小板减少症(ITP)和非 ITP 相关血小板减少症患者中的作用。我们纳入了 190 例 ITP 患者和 94 例非 ITP 相关血小板减少症患者,包括再生障碍性贫血(AA)和骨髓增生异常综合征(MDS)患者。110 名健康志愿者作为对照。我们发现 ITP 或 AA 和 MDS 背景下的血小板减少症患者中去唾液酸化血小板明显增加。血小板去唾液酸化与血小板计数呈负相关。同时,血小板减少症患者的循环 TFH 水平明显高于正常对照组,且与去唾液酸化血小板水平呈正相关。此外,ITP 患者的 TFHs 相关趋化因子 CXCL13 和凋亡血小板水平异常升高。在同一队列中观察到促凋亡蛋白的上调和 MAPK/mTOR 通路的激活。这些发现表明,血小板去唾液酸化和循环 TFHs 可能成为评估 ITP 和非 ITP 患者与血小板减少症相关疾病过程的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c0/9016750/2bb921342a78/fimmu-13-810620-g001.jpg

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