CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(09): 1486-1501
DOI: 10.1055/a-1825-2915
Cellular Haemostasis and Platelets

Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus

1   Section of Rheumatology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Skåne, Sweden
,
Andreas Jern
1   Section of Rheumatology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Skåne, Sweden
,
Helena Tydén
1   Section of Rheumatology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Skåne, Sweden
,
Birgitta Gullstrand
1   Section of Rheumatology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Skåne, Sweden
,
Hong Yan
2   Swedish National Infrastructure for Biological Mass Spectrometry, BioMS, Lund, Sweden
,
Charlotte Welinder
3   Section of Oncology, Clinical Sciences, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Skåne, Sweden
,
Robin Kahn
4   Section of Pediatrics, Department of Clinical Sciences Lund, Wallenberg Center for Molecular Medicine, Lund University, Lund, Skåne, Sweden
,
Andreas Jönsen
1   Section of Rheumatology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Skåne, Sweden
,
John W. Semple
5   Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden
6   Clinical Immunology and Transfusion Medicine, Office of Medical Services, Region Skåne, Lund, Sweden
7   Department of Pharmacology, University of Toronto, Toronto, Canada
,
Anders A. Bengtsson
1   Section of Rheumatology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Skåne, Sweden
› Author Affiliations
Funding This work was supported by grants from the Ulla and Roland Gustafsson foundation, Thelma Zoega Foundation for Medical Research, the Royal Physiographic Society of Lund, the Swedish Research Council (2018–02516), King Gustaf V's 80th Birthday Foundation, Alfred Österlund's Foundation, the Anna-Greta Crafoord Foundation, Greta and Johan Kock's Foundation, Skåne University Hospital, the Swedish Rheumatism Association, and the Medical Faculty of Lund University.


Abstract

Background Systemic lupus erythematosus (SLE) is a complex disease characterized by autoimmunity toward apoptotic cells, excessive amounts of circulating immune complexes, and complement activation. A decreased platelet size has been observed in SLE and their nonhemostatic functions may play an active role in the disease. The main objective of this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome.

Methods Platelets were isolated from 23 patients with SLE. The five individuals with the highest and lowest average platelet forward scatter were selected for further analysis. Platelet protein content was analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) and compared with platelets from five healthy controls. Data are available via ProteomeXchange with identifier PXD031202.

Results Out of 2,572 proteins identified, 396 had significantly different levels (ANOVA q-value ≤ 0.01). Forty proteins, including immunoglobulin-, complement- and phosphatidylserine-binding proteins had higher abundance in platelets from SLE patients, largely independent of size (fold difference of ≥1.5 and a t-test p-value of ≤0.05 as cut-off). Functional characterization revealed increased degranulation and skewed hemostatic balance in platelets from SLE patients. In the SLE proteome, immunoglobulin proteins were negatively correlated to serum complement C3 and C4 and the highest relative levels were detected in platelets of normal size.

Conclusion Platelets from SLE patients shared a specific protein profile, including immunoglobulins, complement proteins, and autoantigens, largely independent of the platelet size and in agreement with an integrated role for platelets in SLE.

Supplementary Material

Supplementary Material



Publication History

Received: 14 September 2021

Accepted: 09 March 2022

Accepted Manuscript online:
13 April 2022

Article published online:
24 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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