研究室について

我々の研究室では、「抗リン脂質抗体症候群の鑑別診断および発症機序の解明」・ 「酸化ストレスに起因する病態発症機序の解明」の2本柱を掲げて、他の研究室や 他大学と共同で研究を進めています。

１. 自己免疫性血栓塞栓症の鑑別診断および発症機序の解明に関する研究

抗リン脂質抗体症候群（APS）は，リン脂質に関連する自己抗体である抗リン脂質抗体の出現と，それに伴う多彩な合併症（脳血管障害・虚血性心疾患・深部静脈血栓症・肺塞栓症・習慣性流死産など）を特徴とする自己免疫疾患であります．我々の研究室は，日本抗リン脂質抗体部会および日本抗リン脂質抗体標準化ワークショップに加盟し，日本におけるAPS検査の標準化を進めると共に，独自でELISAや凝固アッセイを開発し，新たなAPS検査診断法の確立を目指しています．さらに，患者から同定された抗体を単離・精製し，分子レベルで抗リン脂質抗体の血栓形成機序（血小板活性化作用，凝固制御機構阻害作用，単球・好中球・血管内皮細胞における組織因子発現・接着分子発現・NETs形成・サイトカイン産生）の解明に取り組んでいます．

1. Kaneshige R, Nojima J, Motoki Y, Tsuneoka H. aCL/β2GPI and aPS/PT show synergic thrombogenic effects in suppressing anticoagulant activity of APC and stimulating tissue factor expression and TNF-α secretion by mononuclear cells. Thromb Res. 181: 52-58, 2019.
2. Nojima J, Motoki Y, Hara K, Sakata T, Tsuneoka H, Ichihara K. Detection of antibodies against domain 1 of β2-glycoprotein I is key in predicting thromboembolic complications in patients with systemic lupus erythematosus. Thromb Res. 153(6): 83-84, 2017.
3. Nojima J, Motoki Y, Hara K, Sakata T, Ichihara K. Novel enzyme immunoassay system for simultaneous detection of six subclasses of anti-phospholipid antibodies for differential diagnosis of anti-phospholipid syndrome. Blood Coagul Fibrinolysis. 28(4): 316-322, 2017.
4. Motoki Y, Nojima J, Yanagihara M, Tsuneoka H, Matsui T, Yamamoto M, Ichihara K. Anti-phospholipid antibodies contribute to arteriosclerosis in patients with systemic lupus erythematosus through induction of tissue factor expression and cytokine production from peripheral blood mononuclear cells. Thromb Res. 130: 667-673, 2012.
5. Nojima J, Motoki Y, Tsuneoka H, Kuratsune H, Matsui T, Yamamoto M, Yanagihara M, Hinoda Y, Ichihara K. 'Oxidation stress index' as a possible clinical marker for the evaluation of non-Hodgkin lymphoma. Br J Haematol. 155: 528-530, 2011.
6. Nojima J, Masuda Y, Iwatani Y, Kuratsune H, Watanabe Y, Suehisa E, Takano T, Hidaka Y, Kanakura Y. Arteriosclerosis obliterans associated with anti- cardiolipin antibody/β2-glycoprotein I antibodies as a strong risk factor for ischaemic heart disease in patients with systemic lupus erythematosus. Rheumatology 47: 684-689, 2008.
7. Nojima J, Masuda Y, Iwatani Y, Suehisa E, Futsukaichi Y, Kuratsune H, Watanabe Y, Takano T, Hidaka Y, Kanakura Y. Tissue factor expression on monocytes induced by anti-phospholipid antibodies as a strong risk factor for thromboembolic complications in SLE patients. Biochem Biophys Res Commun. 365: 195-200, 2008.
8. Nojima J, Sakudo A, Hakariya Y, Kuratsune H, Watanabe Y, Kanakura Y, Ikuta K. Spectroscopic diagnosis of anti-phospholipid antibodies by visible and near-infrared spectroscopy in SLE patients' plasma samples. Biochem Biophys Res Commun. 362: 522-524, 2007.
9. Nojima J, Iwatani Y, Suehisa E, Kuratsune H, Kanakura Y. The presence of anti-phosphatidyl-serine/prothrombin antibodies is the strongest risk factor for both arterial and venous thrombosis in patients with systemic lupus erythematosus. Haematologica. 91: 699-702, 2006.
10. Nojima J, Kuratsune H, Suehisa E, Iwatani Y, Kanakura Y. Acquired activated protein C resistance associated with IgG antibodies against β2-glycoprotein I and prothrombin as a strong risk factor for venous thromboembolism. Clin Chem. 51: 545-552, 2005.
11. Nojima J, Kuratsune H, Suehisa E, Kitani T, Iwatani Y, Kanakura Y. Strong correlation between the prevalence of cerebral infarction and the presence of anti-cardiolipin /β2-glycoprotein I and anti-phosphatidylserine /prothrombin antibodies. Thromb Haemost. 91: 967-976, 2004.
12. Nojima J, Kuratsune H, Suehisa E, Kawasaki T, Machii T, Kitani T, Iwatani Y, Kanakura Y. Acquired activated protein C resistance associated with anti-protein S antibody as a strong risk factor for deep vein thrombosis in non-SLE patients. Thromb Haemost. 88: 716-722, 2002.
13. Nojima J, Kuratsune H, Suehisa E, Kawasaki T, Machii T, Kitani T, Iwatani Y, Kanakura Y. Acquired activated protein C resistance is associated with the co-existence of anti-prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus. Br J Haematol. 118: 577-583, 2002.
14. Nojima J, Kuratsune H, Suehisa E, Futsukaichi Y, Yamanishi H, Machii T, Kitani T, Iwatani Y, Kanakura Y. Anti-prothrombin antibodies combined with lupus anticoagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus. Br J Haematol. 114: 647-654, 2001.
15. Nojima J, Kuratsune H, Suehisa E, Futsukaichi Y,Yamanishi H,Machii T,Iwatani Y,Kanakura Y. Association between the prevalence of antibodies to β2-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications. Clin Chem. 47: 1008-1015, 2001.
16. Nojima J, Suehisa E, Kuratsune H, Machii T, Koike T, Kitani T, Kanakura Y, Amino N. Platelet activation induced by combined effects of anticardiolipin and lupus anticoagulant IgG antibodies in patients with systemic lupus erythematosus. Thromb Haemost. 81: 436-441, 1999.
17. Nojima J, Suehisa E, Kuratsune H, Machii T, Toku M, Tada H, Yamaguti K, Koike T, Kanakura Y, Kitani T, Amino N. High prevalence of thrombocytopenia in SLE patients with a high levels of anticardiolipin antibodies combined with lupus anticoagulant. Am J Hematol. 58: 55-60, 1998.· 
18.  Nojima J, Suehisa E, Akita N, Toku M, Fushimi R, Tada H, Kuratsune H, Machii T, Kitani T, Amino N. Risk of arterial thrombosis in patients with anticardiolipin antibodies and lupus anticoagulant. Br J Haematol. 96: 447-450, 1997.
19. Ueda E, Kinoshita T, Nojima J, Inoue K, Kitani T. Different membrane anchors of Fc gamma RIII (CD16) on K/NK-lymphocytes and neutrophils. Protein- vs lipid-anchor. J Immunol. 143: 1274-1277, 1989.

我々の研究室は，厚生労働省研究班（AMED研究）に加盟し，理化学研究所・大阪市立大学との共同研究により、 以下の①～③の研究を進行中です．

①慢性疲労症候群（CFS）の客観的診断法の確立と治療効果判定．

②脳内炎症が確認されたCFS患者に対するミクログリア活性化抑制薬の有効性を相対的酸化ストレス度およびFACS解析から検証．

③「健康⇒未病⇒疾患発症」の過程において，迅速かつ客観的に「未病」状態を鑑別できる未病指標を酸化ストレス・抗酸化能力評価の観点から検証．