Journal article

Publication year: 2019

Pages: 1237-1243

Journal: Haematologica

Volume number: 104

Issue number: 6

ISSN: 0390-6078

Open access status: Gold

DOI Link: https://doi.org/10.3324/haematol.2018.211086

Publisher: Ferrata Storti Foundation

Abstract: 
Platelet autoantibody-induced platelet clearance represents a major pathomechanism in immune thrombocytopenia (ITP). There is growing evidence for clinical differences between anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib/IX mediated ITP. Glycoprotein V is a well characterized target antigen in Varicella-associated and drug-induced thrombocytopenia. 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 autoantibodies 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 indirect 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 eliminated 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 suggest that further studies including glycoprotein V will be required before ITP treatment can be tailored according to platelet autoantibody specificity.

Harvard Citation style: Vollenberg, R., Jouni, R., Norris, P., Burg-Roderfeld, M., Cooper, N., Rummel, M., et al. (2019) Glycoprotein V is a relevant immune target in patients with immune thrombocytopenia, Haematologica, 104(6), pp. 1237-1243. https://doi.org/10.3324/haematol.2018.211086

APA Citation style: Vollenberg, R., Jouni, R., Norris, P., Burg-Roderfeld, M., Cooper, N., Rummel, M., Bein, G., Marini, I., Bayat, B., Burack, R., Lazarus, A., Bakchoul, T., & Sachs, U. (2019). Glycoprotein V is a relevant immune target in patients with immune thrombocytopenia. Haematologica. 104(6), 1237-1243. https://doi.org/10.3324/haematol.2018.211086