Autoantibodies to platelet glycoproteins in patients with disease‐related immune thrombocytopenia

Abstract

Although increased platelet destruction and elevated platelet-associated IgG have been shown in patients with lymphomas and various autoimmune diseases, such as systemic lupus erythematosus (SLE), there have been few studies evaluating autoantibodies against platelet-specific antigens. We evaluated 24 patients retrospectively with disease-related thrombocytopenia (12 with lymphoproliferative diseases and 12 with various autoimmune disorders) using a recently reported antigen-specific assay. Autoantibodies against platelet GPIIb/IIIa or GPIb/IX were noted in 15 of the 24 patients (10 of 12 with autoimmune disease and five of 12 with lymphoproliferative disorders). Platelet-associated autoantibodies were present in 60% and plasma autoantibodies in 33%. Anti-GPIIb/IIIa autoantibodies were much more common than those against GPIb/IX. In one patient each with thrombocytopenia and either SLE or myasthenia gravis, absorption of plasma with platelets completely removed the anti-GPIIb/IIIa autoantibodies, but did not affect the level of anti-cochlear autoantibody involved with immune-mediated hearing loss in the SLE patient or the anti-acetylcholine receptor autoantibody in the myasthenic patient. These findings show that, in some cases of disease-related immune thrombocytopenia, autoantibodies against GPIIb/IIIa or GPIb/IX can be detected similar to those seen in chronic ITP. As shown in two patients with multiple autoimmune manifestations, the various autoantibodies have diverse specificities and do not crossreact.

Antibody against platelet membrane glycoprotein VI in a patient with systemic lupus erythematosus

“…Antibodies against a variety of platelet proteins, particularly the GPIIb/IIIa complex, are often seen in patients with SLE [17][18][19] and may be related to the thrombocytopenia in these patients. In this paper, we will present the first case of SLE who acquired a platelet-aggregating anti-GPVI antibody and showed a defective collagen-induced platelet aggregation.…”

Autoimmune Thrombocytopenia

“…Detection of antibodies has revealed that GP IIbIIIa and GP IbIX are the most immunogenic of the platelet glycoproteins (van Leeuwen et al, 1982;Beardsley et al, 1984;Woods et al, 1984a & b;McMillan et al, 1987;Tomiyama et al, 1987Tomiyama et al, & 1989Berchtold et al, 1989a;Kokawa et al, 1993;Deckmyn et al, 1994;He et al, 1994;Stockelberg et al, 1995;Kiefel et al, 1996).…”

“…Nevertheless, the detection of direct platelet eluates requires a selected patient population with a relatively high platelet count. Immunobead assay Disease-related TP 19 9 (47) 2 (11) Berchtold et al, 1989c Immunoprecipitation ITP 6 4 Tomiyama et al, 1990 Immunobead assay ITP children ITP adults 41 16 40 (98) 14 (88) 1 (2) 2 (13) Imbach et al, 1991 MAIPA Immune TP 29 21 (72) 22 (28) 14 (48) Kiefel et al, 1991 ELISA ITP 71 25 (35) 10 (14) Kokawa et al, 1991 Immunobead assay ITP In remission 53 17…”

“…Target antigens of platelet autoantibodies have most frequently been studied in the GP IIbIIIa and GP IbIX complexes (van Leeuwen et al, 1982;Beardsley et al, 1984;Woods et al, 1984a & b;McMillan et al, 1987;Tomiyama et al, 1987Tomiyama et al, & 1989Berchtold et al, 1989a;Kokawa et al, 1993). GP IIbIIIa and GP IbIX have been recognised to be the most immunogenic of the platelet glycoproteins, carrying some recognised autoepitopes, as well as the known alloantigens, clinically important polymorphisms (Kunicki & Newman, 1992;Ouwehand & Navarrete, 2000; Table 1).…”

Quantitation of platelet‐specific autoantibodies in platelet eluates of ITP patients measured by a novel ELISA using the purified glycoprotein complexes GPIIb/IIIa and GPIb/IX as antigens

“…Acute ITP is predominantly a disease of childhood, characterized by the abrupt onset of severe thrombocytopenic purpura, which often occurs with a history of viral infection. Most cases are of short duration and recover spontaneously, usually within 1-2 months, but only in 10-20% of the cases, TP becomes chronic, resembling adult ITP (Cohn, 1976;Berchtold et al, 1989).…”