Strong correlation between the prevalence of cerebral infarction and the presence of anti-cardiolipin/beta2-glycoprotein I and anti-phosphatidylserine/prothrombin antibodies--Co-existence of these antibodies enhances ADP-induced platelet activation in vitro.
Cerebral infarction is the most common arterial thromboembolic complication in the anti-phospholipid antibodies (aPL) syndrome. In an effort to clarify the roles of aPL in the pathogenesis of cerebral infarction in patients with SLE, we examined the levels of anti-cardiolipin/2-glycoprotein I antibodies (anti-CL/beta2-GPI) and anti-phosphatidylserine/prothrombin anti-bodies (anti-PS/PT) in addition to lupus anticoagulant (LA) activity in 126 patients with SLE (35 with cerebral infarction and 91 without thrombosis). Both anti-CL/beta2-GPI and anti-PS/PT strongly correlated with the presence of LA activity. The prevalence of cerebral infarction was obviously higher in the patients who had both anti-CL/beta2-GPI and anti-PS/PT (76.5% [26/34 cases], p<0.0001) than in the other patients having anti-CL/beta2-GPI or anti-PS/PT alone or neither of them (9.8% [9/92 cases]). Furthermore, we studied the in vitro effects of anti-CL/beta2-GPI and/or anti-PS/PT on the enhancement of platelet activation induced by stimulation with a low concentration of adenosine diphosphate (ADP). The purified IgG containing both anti-CL/beta2-GPI and anti-PS/PT caused significant enhancement of platelet activation caused by ADP. However, the purified IgG containing either anti-CL/beta2-GPI or anti-PS/PT had no enhancing effects on it. Furthermore, platelet activation was generated by the mixture of anti-CL/beta2-GPI-IgG and anti-PS/PT-IgG prepared from individual patients, but not by each fraction alone. These results indicate that anti-CL/beta2-GPI and anti-PS/PT may cooperate to promote platelet activation, which may contribute to the risk of cerebral infarction in patients with SLE.
Nojima
Junzo
J
Laboratory for Clinical Investigation, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan. nojima@hp-lab.med.osaka-u.ac.jp
Kuratsune
Hirohiko
H
Suehisa
Etsuji
E
Kitani
Teruo
T
Iwatani
Yoshinori
Y
Kanakura
Yuzuru
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000097:blood / Q000209:etiology* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D016682:Lupus Coagulation Inhibitor / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000276:immunology / Q000378:metabolism; D015539:Platelet Activation / Q000276:immunology; D015995:Prevalence; D011516:Prothrombin / Q000276:immunology / Q000378:metabolism; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D010718:Phosphatidylserines; D053482:beta 2-Glycoprotein I; D011516:Prothrombin