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

BACKGROUND

Glanzmann thrombasthenia (GT) is an inherited platelet function disorder caused by mutations in the fibrinogen receptor αIIbβ3. 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 αIIb and β3, little is known about the proteomic landscape of platelets from GT patients.

OBJECTIVES

To evaluate the platelet proteome in GT.

METHODS

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. αIIbβ3 expression was quantified with whole blood flow cytometry. Medical ethics committee approval was obtained and all participants provided informed consent.

RESULTS

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 αIIb expression correlated well with αIIb 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 αIIbβ3, fibrinogen, and plasminogen. Upregulated proteins were mostly plasma proteins annotated to blood microparticles.

CONCLUSION

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