{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:05:37Z","timestamp":1782777937509,"version":"3.54.5"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T00:00:00Z","timestamp":1418947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In 1983, Graham Hughes first described the concept of antiphospholipid syndrome (APS). In 1984, we described the enzyme\u2010linked immunosorbent assay (ELISA) system which directly detected circulating aCL in patients with systemic lupus erythematosus (SLE) who revealed biological false positive serological test for syphilis. In 1990, three groups, including our group, independently reported the necessity of a cofactor for the binding of autoimmune anticardiolipin antibodies (aCL) to the solid phase phospholipids. \u03b22\u2010glycoprotein I (\u03b22GPI) was identified as this cofactor. In 1994,the epitope for aCL was shown to develop when \u03b22GPI is adsorbed on polyoxygenated polystyrene plates. In 2000, we described antiprothrombin antibodies bind to prothrombin exposed to immobilized phosphatidylserine and established a phosphatidylserine dependent monoclonal antiprothrombin antibody. In 2004, a novel role of nicked \u03b22GPI was identified in the negative feedback pathway of extrinsic fibrinolysis. Nicked \u03b22GPI was found to bind angiostatin 4.5 and to attenuate its antiangiogenic property. In 2004, we demonstrated that the p38 MAPK pathway mediates induction of the TF gene in stimulated with human monoclonal anti\u2010 \u03b22GPI antibodies. Very recently, \u03b22GPI was identified as a complement regulator. The cross\u2010link between complement activation and prothrombotic status in patients with APS has been drawn much attention. Genetic factors are hypothesized to play a role in the susceptibility to APS based on several family studies in patients with antiphospholipid antibodies (aPL) and\/or clinical manifestations of APS. The genetics of \u03b22GPI has been extensively studied. 247 Val\/Leu polymorphism can affect the conformational change of \u03b22\u2010GPI and the exposure of the epitopes for aCL. We found that 247 Val was correlated with anti\u2010\u03b22\u2010GPI production in patients with primary APS, and 247 Val may be important for \u03b22\u2010GPI antigenicity. STAT4 SNP in Japanese patients with SLE and\/or APS. T allele frequencies in SLE and APS were significantly elevated compared with that in healthy controls. When analyzed only in primary APS patients, T allele frequency was further higher. BANK1, BLK and SNP in 1q25.1 region were associated with not only SLE but also APS in Japanese population. These results suggest that APS and SLE, in part, share a common genetic background.<\/jats:p>","DOI":"10.1111\/1756-185x.12438","type":"journal-article","created":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T11:07:59Z","timestamp":1418987279000},"page":"233-241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Antiphospholipid syndrome: 30\u00a0years and our contribution"],"prefix":"10.1111","volume":"18","author":[{"given":"Takao","family":"Koike","sequence":"first","affiliation":[{"name":"Department of Medicine II Hokkaido University Graduate School of Medicine Sapporo Japan"},{"name":"NTT Sapporo Medical Center Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.287.6399.1088"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(83)91267-9"},{"key":"e_1_2_7_4_1","first-page":"193","article-title":"Antiphospholipid antibodies and biological false positive serological test for syphilis in patients with systemic lupus erythematosus","volume":"56","author":"Koike T","year":"1984","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_7_5_1","first-page":"1","article-title":"Crossreactivity of antiphospholipid antibodies","volume":"16","author":"Harris EN","year":"1985","journal-title":"J Clin Lab Immunol"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.11.4120"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91374-J"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91697-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.2.457"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.12.3640"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00114a012"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/3.12.1217"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2770387"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00217367"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050465"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199906)42:6<1189::AID-ANR15>3.0.CO;2-8"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(99)00496-7"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1182\/blood.V96.4.1594","article-title":"Coagulation and fibrinolytic activities in 2 siblings with beta(2)\u2010glycoprotein I deficiency","volume":"96","author":"Takeuchi R","year":"2000","journal-title":"Blood"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2712"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-190629"},{"key":"e_1_2_7_21_1","first-page":"477","article-title":"Quantitative analysis of myocardial infarction in (NZW x BXSB)F1 hybrid mice with systemic lupus erythematosus and small coronary artery disease","volume":"129","author":"Yoshida H","year":"1987","journal-title":"Am J Pathol"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.4049\/jimmunol.149.3.1063","article-title":"Anticardiolipin antibodies in NZW x BXSB F1 mice. 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