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Platelet Biology & Its Disorders
Glycoprotein V is a relevant immune target in patients with immune thrombocytopenia
Richard Vollenberg,1 Rabie Jouni,2 Peter A. A. Norris,3
Monika Burg-Roderfeld,4 Nina Cooper,1 Mathias J. Rummel,5 Gregor Bein,1 Irene Marini,2 Behnaz Bayat,1 Richard Burack,6 Alan H. Lazarus,3
Tamam Bakchoul2* and Ulrich J. Sachs1,7*
1Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany; 2Center for Clinical Transfusion Medicine, Medical Faculty of Tübingen, Eberhard Karls University, Tübingen, Germany; 3The Canadian Blood Services & The Keenan Research Centre of St. Michael's Hospital, Toronto, ON, Canada; 4Faculty for Chemistry and Biology, Fresenius University of Applied Sciences, Idstein, Germany;
5IVth Department of Internal Medicine (Hematology/Oncology), Justus Liebig University, Giessen, Germany; 6Department of Pathology and Laboratory Medicine, University of Rochester, NY, USA and 7Center for Transfusion Medicine and Hemotherapy and Hemostasis Center, University Hospital Giessen and Marburg, Marburg, Germany
ABSTRACT
Platelet autoantibody-induced platelet clearance represents a major pathomechanism in immune thrombocytopenia (ITP). There is grow- ing evidence for clinical differences between anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib/IX mediated ITP. Glycoprotein V is a well charac- terized target antigen in Varicella-associated and drug-induced thrombocy- topenia. We conducted a systematic study assessing the prevalence and functional capacity of autoantibodies against glycoprotein V. A total of 1140 patients were included. In one-third of patients, platelet-bound autoanti- bodies against glycoproteins Ib/IX, IIb/IIIa, or V were detected in a mono- clonal antibody immobilization of platelet antigen assay; platelet-bound autoanti-glycoprotein V was present in the majority of samples (222 out of 343, 64.7%). Investigation of patient sera revealed the presence of free autoantibodies against glycoprotein V in 13.5% of these patients by an indi- rect monoclonal antibody immobilization of platelet antigen assay, but in 39.6% by surface plasmon resonance technology. These antibodies showed significantly lower avidity (association/dissociation ratio 0.32±0.13 vs. 0.73±0.14; P<0.001). High- and low-avidity antibodies induced comparable amounts of platelet uptake in a phagocytosis assay using CD14+ positively- selected human macrophages [mean phagocytic index, 6.81 (range, 4.75- 9.86) vs. 6.01 (range, 5.00-6.98); P=0.954]. In a NOD/SCID mouse model, IgG prepared from both types of anti-glycoprotein V autoantibodies elimi- nated human platelets with no detectable difference between the groups from the murine circulation [mean platelet survival at 300 minutes, 40% (range, 27-55) vs. 35% (16-46); P=0.025]. Our data establish glycoprotein V as a relevant immune target in immune thrombocytopenia. We would sug- gest that further studies including glycoprotein V will be required before ITP treatment can be tailored according to platelet autoantibody specificity.
Introduction
Immune thrombocytopenia (ITP) is an acquired hemorrhagic autoimmune dis- ease characterized by isolated thrombocytopenia.1,2 Autoantibodies against platelet membrane glycoproteins cause platelet destruction and insufficient compensatory platelet production in the bone marrow (BM).3-5 Cytotoxic effects of T cells have also been described.6 Phagocytosis of antibody-decorated platelets via Fc-receptors or, following complement activation, via complement receptors were long-accepted concepts for the understanding of platelet destruction.6,7 Recent studies have pro-
Ferrata Storti Foundation
*TB and UJS contributed equally to this work
Haematologica 2019 Volume 104(6):1237-1243
Correspondence:
ULRICH J. SACHS
ulrich.sachs@med.uni-giessen.de
Received: November 5, 2018. Accepted: March 20, 2019. Pre-published: March 28, 2019.
doi:10.3324/haematol.2018.211086
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/6/1237
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