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

TiN study group and SYMPHONY consortium; Minka Zivkovic; Tatiana M Shamorkina; Maaike W Blaauwgeers; Harm Post; Albert J R Heck; Roger E G Schutgens; Rolf T Urbanus

doi:10.1016/j.jtha.2025.04.004

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

TiN study group and SYMPHONY consortium, Minka Zivkovic, Tatiana M Shamorkina, Maaike W Blaauwgeers, Harm Post, Albert J R Heck, Roger E G Schutgens, Rolf T Urbanus^*

^*Corresponding author for this work

Utrecht University

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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). This 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 people with GT.

AIMS: To evaluate the platelet proteome in GT.

METHODS: Label-free quantification of platelet proteins was performed in thirteen genetically confirmed GT patients (11 type I and 2 type III) and thirteen healthy controls with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). αIIbβ3 expression was quantified with whole blood flow cytometry. Medical ethics committee approval was obtained and all participants provided informed consent.

RESULTS: 2677/3664 identified proteins were considered quantified. Dynamic range spanned 5 orders of magnitude, and the mean CV was 1.2%, indicating data were robust. Flow cytometry-based αIIb expression correlated well with ITGA2B abundance according to LC-MS/MS. Twentynine proteins were less abundant, and 32 proteins were more abundant in GT than in controls. Downregulated proteins were enriched for alpha (α)-granule proteins, including SPARC, APLP2, TIMP1 and TLT-1 in addition to the subunits of integrin αIIbβ3, fibrinogen and plasminogen. Unregulated proteins were mostly plasma proteins annotated to blood microparticles.

CONCLUSION: Glanzmann thrombasthenia platelets show reduced abundance of specific platelet α-granule proteins compared with healthy controls.

Original language	English
Journal	Journal of Thrombosis and Haemostasis
DOIs	https://doi.org/10.1016/j.jtha.2025.04.004
Publication status	E-pub ahead of print - 14 Apr 2025

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TiN study group and SYMPHONY consortium, Zivkovic, M., Shamorkina, T. M., Blaauwgeers, M. W., Post, H., Heck, A. J. R., Schutgens, R. E. G., & Urbanus, R. T. (2025). Proteomic analysis indicates lower abundance of platelet alpha-granule proteins in Glanzmann thrombasthenia. Journal of Thrombosis and Haemostasis. Advance online publication. https://doi.org/10.1016/j.jtha.2025.04.004

@article{e6ac1b65e9e2488b9127092deb002bfe,

title = "Proteomic analysis indicates lower abundance of platelet alpha-granule proteins in Glanzmann thrombasthenia",

abstract = "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). This 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 people with GT.AIMS: To evaluate the platelet proteome in GT.METHODS: Label-free quantification of platelet proteins was performed in thirteen genetically confirmed GT patients (11 type I and 2 type III) and thirteen healthy controls with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). αIIbβ3 expression was quantified with whole blood flow cytometry. Medical ethics committee approval was obtained and all participants provided informed consent.RESULTS: 2677/3664 identified proteins were considered quantified. Dynamic range spanned 5 orders of magnitude, and the mean CV was 1.2%, indicating data were robust. Flow cytometry-based αIIb expression correlated well with ITGA2B abundance according to LC-MS/MS. Twentynine proteins were less abundant, and 32 proteins were more abundant in GT than in controls. Downregulated proteins were enriched for alpha (α)-granule proteins, including SPARC, APLP2, TIMP1 and TLT-1 in addition to the subunits of integrin αIIbβ3, fibrinogen and plasminogen. Unregulated proteins were mostly plasma proteins annotated to blood microparticles.CONCLUSION: Glanzmann thrombasthenia platelets show reduced abundance of specific platelet α-granule proteins compared with healthy controls.",

author = "{TiN study group and SYMPHONY consortium} and Minka Zivkovic and Shamorkina, {Tatiana M} and Blaauwgeers, {Maaike W} and Harm Post and Heck, {Albert J R} and Schutgens, {Roger E G} and Urbanus, {Rolf T}",

year = "2025",

month = apr,

day = "14",

doi = "10.1016/j.jtha.2025.04.004",

language = "English",

journal = "Journal of Thrombosis and Haemostasis",

issn = "1538-7933",

publisher = "Elsevier BV",

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TY - JOUR

T1 - Proteomic analysis indicates lower abundance of platelet alpha-granule proteins in Glanzmann thrombasthenia

AU - TiN study group and SYMPHONY consortium

AU - Zivkovic, Minka

AU - Shamorkina, Tatiana M

AU - Blaauwgeers, Maaike W

AU - Post, Harm

AU - Heck, Albert J R

AU - Schutgens, Roger E G

AU - Urbanus, Rolf T

PY - 2025/4/14

Y1 - 2025/4/14

N2 - 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). This 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 people with GT.AIMS: To evaluate the platelet proteome in GT.METHODS: Label-free quantification of platelet proteins was performed in thirteen genetically confirmed GT patients (11 type I and 2 type III) and thirteen healthy controls with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). αIIbβ3 expression was quantified with whole blood flow cytometry. Medical ethics committee approval was obtained and all participants provided informed consent.RESULTS: 2677/3664 identified proteins were considered quantified. Dynamic range spanned 5 orders of magnitude, and the mean CV was 1.2%, indicating data were robust. Flow cytometry-based αIIb expression correlated well with ITGA2B abundance according to LC-MS/MS. Twentynine proteins were less abundant, and 32 proteins were more abundant in GT than in controls. Downregulated proteins were enriched for alpha (α)-granule proteins, including SPARC, APLP2, TIMP1 and TLT-1 in addition to the subunits of integrin αIIbβ3, fibrinogen and plasminogen. Unregulated proteins were mostly plasma proteins annotated to blood microparticles.CONCLUSION: Glanzmann thrombasthenia platelets show reduced abundance of specific platelet α-granule proteins compared with healthy controls.

AB - 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). This 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 people with GT.AIMS: To evaluate the platelet proteome in GT.METHODS: Label-free quantification of platelet proteins was performed in thirteen genetically confirmed GT patients (11 type I and 2 type III) and thirteen healthy controls with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). αIIbβ3 expression was quantified with whole blood flow cytometry. Medical ethics committee approval was obtained and all participants provided informed consent.RESULTS: 2677/3664 identified proteins were considered quantified. Dynamic range spanned 5 orders of magnitude, and the mean CV was 1.2%, indicating data were robust. Flow cytometry-based αIIb expression correlated well with ITGA2B abundance according to LC-MS/MS. Twentynine proteins were less abundant, and 32 proteins were more abundant in GT than in controls. Downregulated proteins were enriched for alpha (α)-granule proteins, including SPARC, APLP2, TIMP1 and TLT-1 in addition to the subunits of integrin αIIbβ3, fibrinogen and plasminogen. Unregulated proteins were mostly plasma proteins annotated to blood microparticles.CONCLUSION: Glanzmann thrombasthenia platelets show reduced abundance of specific platelet α-granule proteins compared with healthy controls.

U2 - 10.1016/j.jtha.2025.04.004

DO - 10.1016/j.jtha.2025.04.004

M3 - Article

C2 - 40239810

SN - 1538-7933

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

ER -

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

Abstract

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