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

Abstract

Background SLE is a complex disease characterized by autoimmunity towards apoptotic cells, excessive amounts of circulating immune complexes and complement activation. Decreased platelet size has been observed in SLE and their non-hemostatic functions may play an active role in the disease. Our main objective in this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome. Methods and patients Platelets were isolated from 23 patients with SLE. The five individuals with 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 to platelets from five healthy controls (HC) Data are available via ProteomeXchange with identifier PXD031202. Results Out of 2572 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 was 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 platelet size and in agreement with an integrated role for platelets in SLE.

Reticulated Platelets: A Promising Prognosis Marker in Cardiovascular Diseases

“…Approximately 100 billion new platelets must be produced daily from megakaryocytes to maintain a physiological platelet count; and the production rate is even higher in patients with sympathetic stress, inflammation and in several acute and chronic diseases including acute myocardial infarction (3,4). Indeed, platelet abnormalities have also been implicated in adverse outcomes in other non-cardiovascular conditions (5,6). Various pathophysiological mechanisms for the adverse impact of activated platelets have recently been reviewed (7)(8)(9).…”

“…3,4 Indeed, platelet abnormalities have also been implicated in adverse outcomes in other noncardiovascular conditions. 5,6 Various pathophysiological mechanisms for the adverse impact of activated platelets have recently been reviewed. [7][8][9] RPs are newly formed platelets (immature) with high granule content and a residual amount of megakaryocytederived mRNA.…”

“…3 4 Indeed, platelet abnormalities have also been implicated in adverse outcomes in other noncardiovascular conditions. 5 6 Various pathophysiological mechanisms for the adverse impact of activated platelets have recently been reviewed. 7 8 9…”