Pathogenesis of antiphospholipid antibodies:

抗磷脂抗体的发病机制：

• 批准号: 17390286
• 负责人: KOIKE Takao
• 金额: $ 9.79万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390286/
• 关键词: Antiphospholipid syndrome; Thrombosis; proteome; p38 MAPK; Integrin; β_2GPI; 免疫学; バイオテクノロジー; p38MARK; Tissue Factor(TF); 抗リン脂質抗体

The antiphospholipid syndrome (APS) is characterized by thrombosis and the presence of antiphospholipid antibodies (aPL). Tissue factor (TF), the major initiator of the coagulation system, is induced on monocytes by aPL in vitro, explaining, in part, the pathophysiology in this syndrome. Recently, it has been focused the nature of the aPL-induced signal transduction pathways leading to TF expression, and we reported that the mitogen-activated protein kinase (MAPK) pathway played an important role in aPL-induced TF expression on monocytes. In this study, we demonstrate that β_2 glycoprotein I (β_2GPI) interacts with plasma gelsolin that binds to integrin5β1 through fibronectin. The interaction between β_2GPI/monoclonal anti-β_2GPI antibody (β_2GPI dependent anticardiolipin antibodies; aCL/β_2GPI) complex and cell surface enhanced in the presence of plasma gelsolin. Western blotting studies using monocyte cell line (RAW264.7) demonstrated that p38 MAPK protein was phosphorylated by monoclonal aCL/β2GPI treatment, and the phosphorylation was attenuated in the presence of anti-integrinα5β1 antibody. Furthermore, focal adhesion kinase (FAK) that is downstream of fibronectin-integrin signaling pathway was phosphorylated by aPL treatment. These results demonstrated that the integrin-p38 MAPK signaling pathway plays an important role in aPL-induced TF expression on monocytes and suggest that the integrin may be a possible therapeutic target to modify a prothrombotic state in patients with APS

抗磷脂综合征(APS)的特征是血栓形成和抗磷脂抗体(APL)的存在。APL在体外诱导单核细胞产生凝血系统的主要起始物组织因子，部分解释了该综合征的病理生理机制。近年来，APL诱导Tf表达的信号转导途径的本质已成为人们关注的焦点，我们报道了丝裂原活化蛋白激酶(MAPK)通路在APL诱导单核细胞Tf表达中起重要作用。在本研究中，我们证明了β_2糖蛋白I(β_2GPI)与血浆明胶蛋白相互作用，而血浆明胶蛋白通过纤维连接蛋白与整合素5β1结合。β_2GPI/抗β_2GPI单抗(β_2GPI依赖的抗心磷脂抗体；β_2GPI)与细胞表面的相互作用在血浆明胶的存在下增强。用单核细胞系RAW 2 6 4.7进行的Western blotting研究表明，单抗acl/β2GPI可使p38MAPK蛋白磷酸化，而在抗整合素α5β1抗体的存在下，这种磷酸化作用减弱。此外，APL处理后，位于纤维连接蛋白-整合素信号通路下游的粘着斑激酶(FAK)被磷酸化。这些结果表明整合素-p38MAPK信号通路在APL诱导的单核细胞TF表达中起重要作用，提示整合素可能是改变APS患者血栓前状态的一个可能的治疗靶点。

项目成果

Factor Xa inhibitors : new anti-thrombotic agents and their characteristics.

Xa 因子抑制剂：新型抗血栓药物及其特性。

• 发表时间: 2006
• 期刊: Frontiers in Bioscience 11
• 作者: Ieko M;Tarumi T;Nakabayashi T;Yoshida M;Naito S;Koike T
• 通讯作者: Koike T

Hypogammaglobulinemmia with a selective delayed recovery inmemory B cells and an impaired Isotype expression after rituximab administration as an adjuvant to autologous sterr cell transplantation for non-Hodgkin lymphoma.

利妥昔单抗作为非霍奇金淋巴瘤自体 sterr 细胞移植的佐剂后，出现低丙种球蛋白血症，记忆 B 细胞选择性延迟恢复，同种型表达受损。

• 发表时间: 2006
• 期刊: Eur J Haemato. 77
• 作者: Nishio M;Fujimoto K;Yamamoto S;Endo T;Sakai T;Obara M;Kumano K;Minauchi K;Yamaguchi K;Takeda Y;Sato N;Koizumi K;Mukai M;Koike T.
• 通讯作者: Koike T.

Hypogammaglobulinemmia with a selective delayed recovery inmemory B cells and an impaired Isotype expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma.

利妥昔单抗作为非霍奇金淋巴瘤自体干细胞移植的佐剂后，出现低丙种球蛋白血症，记忆 B 细胞选择性延迟恢复，同种型表达受损。

• 发表时间: 2006
• 期刊: Eur J Haemato. 77
• 作者: Nishio M;Fujimoto K;Yamamoto S;Endo T;Sakai T;Obara M;Kumano K;Minauchi K;Yamaguchi K;Takeda Y;Sato N;Koizumi K;Mukai M;Koike T
• 通讯作者: Koike T

Persistent panhypogammaglobulinemia with selected loss of memory B cells and impaired isotype expression after rituximab therapy for post-transplant EBV-associated autoimmune hemolytic anemia.

利妥昔单抗治疗移植后 EBV 相关自身免疫性溶血性贫血后，出现持续性全低丙种球蛋白血症，伴有选择性记忆 B 细胞丢失和同种型表达受损。

• 发表时间: 2005
• 期刊: Eur J Haematol 75
• 作者: Nishio;M.;Endo;T.;Fujimoto;K.;Sato;N.;Sakai;T.;Obara;M.;Kumano;K.;Minauchi;K.;Koike,T.
• 通讯作者: Koike,T.

Hepatosplenic alpha/beta T cell lymphoma presenting with cold agglutinin disease

伴有冷凝集素病的肝脾 α/β T 细胞淋巴瘤

• 发表时间: 2007
• 期刊: Ann Hematol 86(2)
• 作者: Minauchi K;Nishio M;Itoh T;Yamamoto S;Fujimoto K;Sato N;Koike T.
• 通讯作者: Koike T.