Shedding Of Soluble Glycoprotein Vi Is Neither Affected By Animal-Derived Antibeta-2-Glycoprotein 1 Antibodies Nor Igg Fractions From Patients With Systemic Lupus Erythematosus

Antibeta-2-glycoprotein 1 (anti beta(2)GP1) antibodies are associated with increased risk of thrombosis in patients with systemic lupus erythematosus (SLE). The specific effect(s) of anti beta(2)GP1 antibodies on platelets are unclear. Platelet activation in response to antiplatelet antibodies has been shown to induce shedding of the ectodomain of the platelet collagen receptor, glycoprotein VI (GPVI), releasing soluble GPVI (sGPVI). The aim of this study was to therefore determine whether anti beta(2)GP1 antibodies, and/or purified IgG fractions, from patients with SLE shed sGPVI from platelets. We determined sGPVI levels in platelet poor plasma from SLE patients with/without anti beta(2)GP1 antibodies (nU37), as well as in platelet-rich plasma from healthy donors treated with either SLE-derived IgG fractions containing anti beta(2)GP1, animal-derived anti beta(2)GP1, or isotype control antibodies. Levels of sGPVI were higher in three SLE-derived platelet poor plasma with anti beta(2)GP1 antibodies (103.52 +/- 12.32 ng/ml) compared with those without (28.11 +/- 12.73 ng/ml). Neither SLE-derived IgG fractions containing anti beta(2)GP1 antibodies, nor animalderived anti beta(2)GP1 antibodies induced significant shedding of sGPVI from healthy donor platelets compared with isotype controls. These results suggest that anti beta(2)GP1 antibodies do not affect shedding of sGPVI, and therefore collagen-mediated platelet signalling pathways. The shedding activity in SLE patients may be due to factors other than anti beta(2)GP1 antibodies, for example, metalloproteinases. Copyright (C) 2020 Wolters Kluwer Health, Inc. All rights reserved.