Proteomic analysis indicates lower abundance of platelet α-granule proteins in Glanzmann thrombasthenia
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background Glanzmann thrombasthenia (GT) is an inherited platelet function disorder caused by mutations in the fibrinogen receptor α IIb β 3 . 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 β 3 , 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. α IIb β 3 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 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 IIb β 3 , 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.
Authors: Minka Zivkovic, Tatiana M. Shamorkina, Maaike W. Blaauwgeers, Harm Post, Albert J.R. Heck, Roger E.G. Schutgens, Rolf T. Urbanus, Rolf T. Urbanus, Erik Beckers, Michiel Coppens, Jeroen Eikenboom, Louise Hooimeijer, Gerard Jansen, Roger Schutgens, Rolf Urbanus, Rolf Urbanus, Minka Zivkovic, Emile van den Akker, Wala Al Arashi, Ryanne Arisz, Lieke Baas, Ruben Bierings, Maartje van den Biggelaar, Johan Boender, Anske van der Bom, Mettine Bos, Martijn Brands, Annelien Bredenoord, Laura Bukkems, Lex Burdorf, Jessica Del Castillo Alferez, Michael Cloesmeijer, Marjon Cnossen, Mariëtte Driessens, Jeroen Eikenboom, Karin Fijnvandraat, Kathelijn Fischer, Geertje Goedhart, Tine Goedhart, Samantha Gouw, Rieke van der Graaf, Masja de Haas, Lotte Haverman, Jan Hazelzet, Shannon van Hoorn, Elise Huisman, Nathalie Jansen, Alexander Janssen, Sean de Jong, Sjoerd Koopman, Marieke Kruip, Sebastiaan Laan, Frank Leebeek, Nikki van Leeuwen, Hester Lingsma, Moniek de Maat, Ron Mathôt, Felix van der Meer, Karina Meijer, Sander Meijer, Stephan Meijer, Iris van Moort, Caroline Mussert, Hans Kristian Ploos van Amstel, Suzanne Polinder, Diaz Prameyllawati, Simone Reitsma, Eliza Roest, Lorenzo Romano, Saskia Schols, Roger Schutgens, Rolf Urbanus, Rolf Urbanus, Carin Uyl, Jan Voorberg, Huan Zhang, Minka Zivkovic
Institutions: Utrecht University, University Medical Center Utrecht
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,750
OpenAlex ID: W4409429823