Presence of platelet-associated anti-glycoprotein (GP)VI autoantibodies and restoration of GPVI expression in patients with GPVI deficiency.
BACKGROUND
Glycoprotein (GP)VI deficiency is a rare platelet disorder with a mild bleeding tendency. However, its pathophysiology remains unclear.


OBJECTIVE
We characterized a novel GPVI-deficient patient with immune thrombocytopenic purpura and searched for the presence of anti-GPVI autoantibodies in this and another patient with GPVI deficiency.


RESULTS
A 12-year-old Japanese girl (case 1) with moderate thrombocytopenia and mild bleeding showed selectively impaired collagen-induced platelet aggregation. Flow cytometric analysis indicated that the patient had a defect in the expression of GPVI-FcRgamma. An eluate of her platelet-associated IgG contained anti-alpha(IIb)beta3 autoantibodies. Moreover, using GPVI-FcRgamma-transfected cells, we unexpectedly identified anti-GPVI antibodies against the soluble ectodomain of GPVI in the eluate, despite the patient's GPVI deficiency. In contrast, anti-GPVI antibodies were not detectable in her plasma. In another case of GPVI deficiency (case 2) without detectable plasma anti-GPVI antibodies, we again detected platelet-associated anti-GPVI antibodies. In a 2-year follow-up of case 1, the platelet count increased to within the normal range and the bleeding tendency improved. Interestingly, GPVI was again expressed on her platelets, in association with a decrease in the relative amount of anti-GPVI antibodies.


CONCLUSIONS
This is the first demonstration of platelet-associated anti-GPVI antibodies in GPVI-deficient subjects, in one case with spontaneous restoration of GPVI expression. These results strongly suggest an autoimmune mechanism in GPVI deficiency.
Akiyama
M
M
Department of Haematology and Oncology, Graduate School of Medicine C9, Osaka University, Osaka, Japan.
Kashiwagi
H
H
Todo
K
K
Moroi
M
M
Berndt
M C
MC
Kojima
H
H
Kanakura
Y
Y
Tomiyama
Y
Y
D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D001792:Blood Platelets / Q000276:immunology*; D002648:Child; D000939:Epitopes; D005260:Female; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology
D001323:Autoantibodies; D000939:Epitopes; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI