Presence of platelet-associated anti-glycoprotein (GP)VI autoantibodies and restoration of GPVI expression in patients with GPVI deficiency.

Glycoprotein (GP)VI deficiency is a rare platelet disorder with a mild bleeding tendency. However, its pathophysiology remains unclear.
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.
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.
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.
AuthorsM Akiyama, H Kashiwagi, K Todo, M Moroi, M C Berndt, H Kojima, Y Kanakura, Y Tomiyama
JournalJournal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 7 Issue 8 Pg. 1373-83 (Aug 2009) ISSN: 1538-7836 [Electronic] England
PMID19522742 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Autoantibodies
  • Epitopes
  • Platelet Membrane Glycoproteins
  • platelet membrane glycoprotein VI
  • Adult
  • Autoantibodies (analysis)
  • Blood Platelets (immunology)
  • Child
  • Epitopes
  • Female
  • Humans
  • Platelet Membrane Glycoproteins (biosynthesis, deficiency, immunology)
  • Purpura, Thrombocytopenic, Idiopathic (immunology)

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