Altered Protein Profiles in Platelets of Lupus Anticoagulant Positive Patients - New Players in LA-related Thrombosis?

Objectives: Patients with lupus anticoagulants (LA) are at high risk to develop thromboembolism (TE). Previous studies have shown that platelets from LA positive patients show an increased activation status. The aim of this study was to gain deeper insights into the role of platelets in the antiphospholipid syndrome by investigating the platelet proteome of LA positive patients with TE (LA+TE+), LA positive patients without TE (LA+TE-) and of healthy controls.

Methods: Platelets from 47 LA positive patients, 31 with a history of TE, 16 without a thrombotic history and 47 healthy controls were analyzed for differences in the proteome with two-dimensional differential in-gel electrophoresis (2D-DIGE). Significantly altered protein spots were identified by mass spectrometry. Selected LA+TE+ related proteins, published to be relevant in thrombosis development, were validated by western blot and ELISA.

Results: Alterations in the abundance of 25 proteins were observed between LA+TE+ individuals, LA+TE- individuals and healthy controls. Unbiased STRING-pathway analysis showed that LA related protein changes are involved in platelet activation, aggregation, and degranulation pathways. Additionally, family members of protein disulfide-isomerase were upregulated in LA+TE+ patients compared with control groups. Leukocyte elastase inhibitor, involved in the cross talk between platelets and neutrophils, was downregulated in LA+TE+ patients compared with healthy controls, corresponding to the increased citrullinated histone 3 levels, indicating neutrophil extracellular trap formation, in patients with LA and history of TE.

Conclusions: Our findings demonstrate protein abundance changes of platelets in LA positive patients, described to be connected with altered platelet function, especially in those with a history of TE. These LA-related platelet protein profiles suggest a causative role of platelets in the development of thrombosis in those patients.

No conflict of interest has been declared by the author(s).