IgG from patients with antiphospholipid syndrome binds to platelets without induction of platelet activation.
The clinical manifestations of the antiphospholipid syndrome (APLS) include arterial and venous thrombosis, thrombocytopenia and fetal loss, but the pathogenic mechanisms remain unclear. It has been hypothesized that platelet activation by autoantibody may be a pathogenic mechanism. We studied IgG binding, microparticle (mp) formation and P-selectin expression by flow cytometry in normal platelets after incubation in serum from 11 patients with antiphospholipid antibodies and that from 10 normal healthy subjects. Levels of platelet-associated IgG were significantly higher after incubation in patient sera (mean 17.2, range 2.0-75.0%) compared with normal sera (mean 2.0, range 1.2-3.7%, P<0.05). Incubation of normal platelets in serum led to increased microparticle formation (P<0.01) and P-selectin expression (P < 0.05), compared with unstimulated platelets. There was no significant difference, however, between microparticle formation nor P-Selectin expression induced by patient serum (mp 3.0 (1.6-5.0)%; P-selectin 8.0 (4.0-16.6)%) versus normal serum (mp 3.2 (2.1-4.5)%; P-selectin 10.1 (4.0-15.6); median (range)). Pre-activation of platelets with sub-threshold ADP concentrations or thrombin receptor activator peptide resulted in a small increase in microparticle formation, but there was still no significant difference between the effects of patient and control sera. Despite the presence of platelet membrane binding IgG in serum from 5/11 patients with antiphospholipid antibodies, there was no evidence for associated enhanced platelet-activating ability. This study supports antiplatelet reactivity in antiphospholipid syndrome, but not a direct platelet-activating role for platelet-directed autoantibodies.
Ford
I
I
Department of Medicine and Therapeutics, University of Aberdeen, Scotland.
Urbaniak
S
S
Greaves
M
M
D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology*
D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D019007:P-Selectin; D002118:Calcium