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

Linge, Carl Petrus LU ; Jern, Andreas LU ; Tydén, Helena LU ; Gullstrand, Birgitta LU ; Yan, Hong LU ; Welinder, Charlotte LU ; Kahn, Robin LU ; Jönsen, Andreas LU ; Semple, John W. LU and Bengtsson, Anders A. LU (2022) In Thrombosis and Haemostasis 122(9). p.1486-1501
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... (More)

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 phosphatidylserinebinding 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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
autoantibodies, complement, immunoglobulins, platelet, SLE
in
Thrombosis and Haemostasis
volume
122
issue
9
pages
16 pages
publisher
Schattauer GmbH
external identifiers
  • pmid:35419777
  • scopus:85135747432
ISSN
0340-6245
DOI
10.1055/a-1825-2915
language
English
LU publication?
yes
id
16f09d3b-7f26-4678-9748-60743b8d4100
date added to LUP
2022-10-11 13:05:52
date last changed
2024-06-27 16:24:16
@article{16f09d3b-7f26-4678-9748-60743b8d4100,
  abstract     = {{<p>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 phosphatidylserinebinding 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.</p>}},
  author       = {{Linge, Carl Petrus and Jern, Andreas and Tydén, Helena and Gullstrand, Birgitta and Yan, Hong and Welinder, Charlotte and Kahn, Robin and Jönsen, Andreas and Semple, John W. and Bengtsson, Anders A.}},
  issn         = {{0340-6245}},
  keywords     = {{autoantibodies; complement; immunoglobulins; platelet; SLE}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{9}},
  pages        = {{1486--1501}},
  publisher    = {{Schattauer GmbH}},
  series       = {{Thrombosis and Haemostasis}},
  title        = {{Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus}},
  url          = {{http://dx.doi.org/10.1055/a-1825-2915}},
  doi          = {{10.1055/a-1825-2915}},
  volume       = {{122}},
  year         = {{2022}},
}