Proteomic analysis indicates lower abundance of platelet α-granule proteins in Glanzmann thrombasthenia

Glanzmann thrombasthenia (GT) is an inherited platelet function disorder caused by mutations in the fibrinogen receptor α_IIbβ₃. The deficiency can be quantitative (type I/II) or qualitative (type III). It causes lack of platelet aggregation and leads to a moderate to severe bleeding tendency. Besides the absence or functional alteration of the integrins α_IIb and β₃, little is known about the proteomic landscape of platelets from GT patients.

To evaluate the platelet proteome in GT.

Label-free quantification of platelet proteins was performed in 13 genetically confirmed GT patients (11 type I and 2 type III) and 13 healthy controls with liquid chromatography coupled with tandem mass spectrometry. α_IIbβ₃ expression was quantified with whole blood flow cytometry. Medical ethics committee approval was obtained and all participants provided informed consent.

Of 3664 identified proteins, 2677 were considered quantified. Dynamic range spanned 5 orders of magnitude, and the mean coefficient of variation was 1.2%, indicating data were robust. Flow cytometry-based α_IIb expression correlated well with α_IIb abundance according to liquid chromatography-tandem mass spectrometry. Twenty-nine proteins were less abundant, and 32 proteins were more abundant in GT patients than in controls. Downregulated proteins were enriched for α-granule proteins, including secreted protein acidic and cyteine rich, amyloid β precursor-like protein 2, TIMP metallopeptidase inhibitor 1, and TREM-like transcript-1, in addition to the subunits of integrin α_IIbβ₃, fibrinogen, and plasminogen. Upregulated proteins were mostly plasma proteins annotated to blood microparticles.

GT platelets show reduced abundance of specific platelet α-granule proteins compared with healthy controls.