Platelet activation induced by an antiplatelet autoantibody against CD9 antigen and its inhibition by another autoantibody in immune thrombocytopenic purpura.
In a patient with immune thrombocytopenic purpura (ITP), we found a novel platelet-activating IgG (act-IgG) and an inhibitory IgG (inhi-IgG) that prevented activation induced by both CD9 monoclonal antibody (mAb) and the act-IgG. Purified IgG from the patient plasma caused a rise in [Ca2+]i and the aggregation of normal platelets, and bound to a 24 kD membrane protein. This aggregation was inhibited by aspirin, staurosporine, an inhibitor of protein kinase C, and F(ab')2 fragments of MALL13, a CD9 mAb. When the platelet count of this patient rose to normal range, the act-IgG disappeared. About 2 weeks later, the relapse of thrombocytopenia was observed. The purified IgG obtained in this period did not activate platelets but inhibited both the rise in [Ca2+]i and platelet aggregation stimulated by NNKY 1-19, a CD9 mAb, as well as the act-IgG, and bound to a 40 kD membrane protein. The inhi-IgG prevented the binding of IV-3, a mAb against Fc gamma receptor II (Fc gamma RII), but did not prevent the binding of NNKY 1-19 to its antigen. We suggest that the activating autoantibody recognized CD9 antigen and activated both the thromboxane- and phospholipase C-dependent pathways, while the inhibitory autoantibody recognized the Fc gamma RII and inhibited CD9 antibody-induced platelet activation mediated via this receptor.
Yanabu
M
M
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Nomura
S
S
Fukuroi
T
T
Suzuki
M
M
Kawakatsu
T
T
Kido
H
H
Yamaguchi
K
K
Kokawa
T
T
Yasunaga
K
K
D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins; D010974:Platelet Aggregation / Q000187:drug effects / Q000276:immunology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology; D060245:Tetraspanin 29
D015703:Antigens, CD; D001323:Autoantibodies; C554869:CD9 protein, human; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D010980:Platelet Membrane Glycoproteins; D017452:Receptors, IgG; D060245:Tetraspanin 29; D002118:Calcium