title: Presence of platelet-associated anti-glycoprotein (GP)VI autoantibodies and restoration of GPVI expression in patients with GPVI deficiency.
abstract: 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.
authors.affiliation: Department of Haematology and Oncology, Graduate School of Medicine C9, Osaka University, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Akiyama
authors.forename: H
authors.initials: H
authors.lastname: Kashiwagi
authors.forename: K
authors.initials: K
authors.lastname: Todo
authors.forename: M
authors.initials: M
authors.lastname: Moroi
authors.forename: M C
authors.initials: MC
authors.lastname: Berndt
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: Y
authors.initials: Y
authors.lastname: Kanakura
authors.forename: Y
authors.initials: Y
authors.lastname: Tomiyama
mesh_terms: 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
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI