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

E.E. Gardiner; M. Al-Tamimi; F.-T. Mu; D. Karunakaran; J.Y. Thom; M. Moroi; R.K. Andrews; M.C. Berndt; R.I. Baker

doi:10.1111/j.1538-7836.2008.03016.x

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

Journal article

Peer reviewed

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

E.E. Gardiner, M. Al-Tamimi, F.-T. Mu, D. Karunakaran, J.Y. Thom, M. Moroi, R.K. Andrews, M.C. Berndt and R.I. Baker

Journal of Thrombosis and Haemostasis, Vol.6(7), pp.1175-1182

2008

DOI: 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.

Details

Title: Compromised ITAM-based platelet receptor function in a patient with immune thrombocytopenic purpura
Authors/Creators: E.E. Gardiner (Author/Creator) - Monash University
M. Al-Tamimi (Author/Creator) - Monash University
F.-T. Mu (Author/Creator) - Monash University
D. Karunakaran (Author/Creator) - Monash University
J.Y. Thom (Author/Creator) - Royal Perth Hospital
M. Moroi (Author/Creator) - Kurume University
R.K. Andrews (Author/Creator) - Monash University
M.C. Berndt (Author/Creator) - Monash University
R.I. Baker (Author/Creator) - Monash University
Publication Details: Journal of Thrombosis and Haemostasis, Vol.6(7), pp.1175-1182
Publisher: Wiley
Identifiers: 991005542722207891
Copyright: © 1999 - 2017 John Wiley & Sons, Inc.
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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52 Times Cited - Web of Science

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.75 Blood Clotting; 1.75.619 Bleeding Disorders
Web Of Science research areas: Hematology; Peripheral Vascular Disease
ESI research areas: Clinical Medicine