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Compromised ITAM-based platelet receptor function in a patient with immune thrombocytopenic purpura

Gardiner, E.E., Al-Tamimi, M., Mu, F.-T., Karunakaran, D., Thom, J.Y., Moroi, M., Andrews, R.K., Berndt, M.C. and Baker, R.I. (2008) Compromised ITAM-based platelet receptor function in a patient with immune thrombocytopenic purpura. Journal of Thrombosis and Haemostasis, 6 (7). pp. 1175-1182.

Free to read: https://doi.org/10.1111/j.1538-7836.2008.03016.x
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Abstract

Background: Receptors on platelets that contain immunoreceptor tyrosine-based activation motifs (ITAMs) include collagen receptor glycoprotein (GP) VI, and FcγRIIa, a low affinity receptor for immunoglobulin (Ig) G. Objectives: We examined the function of GPVI and FcγRIIa in a patient diagnosed with immune thrombocytopenic purpura (ITP) who had unexplained pathological bruising despite normalization of the platelet count with treatment.
Methods and Results: Patient platelets aggregated normally in response to ADP, arachadonic acid and epinephrine, but not to GPVI agonists, collagen or collagen-related peptide, or to FcγRII-activating monoclonal antibody (mAb) 8.26, suggesting ITAM receptor dysfunction. Plasma contained an anti-GPVI antibody by MAIPA and aggregated normal platelets. Aggregating activity was partially (∼60%) blocked by FcγRIIa-blocking antibody, IV.3, and completely blocked by soluble GPVI ectodomain. Full-length GPVI on the patient platelet surface was reduced to ∼10% of normal levels, and a ∼10-kDa GPVI cytoplasmic tail remnant and cleaved FcγRIIa were detectable by western blot, indicating platelet receptor proteolysis. Plasma from the patient contained ∼150 ng mL−1 soluble GPVI by ELISA (normal plasma, ∼15 ng mL−1) and IgG purified from patient plasma caused FcγRIIa-mediated, EDTA-sensitive cleavage of both GPVI and FcγRIIa on normal platelets.
Conclusions: In ITP patients, platelet autoantibodies can curtail platelet receptor function. Platelet ITAM receptor dysfunction may contribute to the increased bleeding phenotype observed in some patients with ITP.

Publication Type: Journal Article
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Publisher: Wiley
Copyright: © 1999 - 2017 John Wiley & Sons, Inc.
URI: http://researchrepository.murdoch.edu.au/id/eprint/37109
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