Department of Clinical Laboratory, Children's Hospital of Soochow University, Suzhou, 215025, Jiangsu Province, China.
BMC Pediatr. 2022 Mar 30;22(1):164. doi: 10.1186/s12887-022-03237-x.
Immune thrombocytopenia (ITP) is the most common etiology of acquired thrombocytopenia diseases in children. ITP is characterized by the immune-mediated decreased formation and excessive destruction of platelets. The pathogenesis and management of pediatric ITP are distinct from adult ITP. A disintegrin and metalloproteinase 17 (ADAM17) mediates the shedding of platelet receptor glycoprotein Ib α (GPIb α) in extracellular domain, functioning in the platelet activation and clearance. Our study aims to probe the roles and mechanisms of ADAM17 in pediatric ITP.
The differently expressed ADAM17 in megakaryocytes was obtained from children with ITP through the next-generation RNA-Sequence. Hematoxylin-eosin and Giemsa staining were performed for cell morphology identification. Flow cytometry was applied to assess autoantibodies against platelets, subtypes of lymphocytes, the surface expression level of ADAM17 and polyploidization of megakaryocytes, as well as the full-length GP Ib α.
ADAM17 was significantly downregulated in megakaryocytes and platelets in children with ITP. Higher values of PDW and positive autoantibodies presence were observed in children with ITP. Loss of ADAM17 in mice led to defects in proplatelet formation and significantly elevated expression of phosphorylated myosin light chain (p-MLC) in megakaryocytes.
Our study indicated that the downregulation of ADAM17 might be an innate cause of inefficient platelet production in pediatric ITP.
免疫性血小板减少症（ITP）是儿童获得性血小板减少症的最常见病因。ITP 的特征是免疫介导的血小板形成减少和过度破坏。儿科 ITP 的发病机制和管理与成人 ITP 不同。解整合素和金属蛋白酶 17（ADAM17）介导血小板受体糖蛋白 Ibα（GPIbα）在细胞外结构域中的脱落，在血小板激活和清除中发挥作用。我们的研究旨在探讨 ADAM17 在儿科 ITP 中的作用和机制。
通过下一代 RNA 测序从 ITP 儿童中获得了差异表达的巨核细胞 ADAM17。苏木精-伊红和吉姆萨染色用于细胞形态鉴定。流式细胞术用于评估针对血小板的自身抗体、淋巴细胞亚群、ADAM17 的表面表达水平和巨核细胞的多倍体化以及全长 GP Ibα。
ADAM17 在 ITP 儿童的巨核细胞和血小板中显著下调。ITP 儿童的 PDW 值较高，且存在阳性自身抗体。在小鼠中缺失 ADAM17 导致前血小板形成缺陷，并显著增加巨核细胞中磷酸化肌球蛋白轻链（p-MLC）的表达。
我们的研究表明，ADAM17 的下调可能是儿科 ITP 中血小板生成效率低下的先天原因。
