Unique Protein Signature of Circulating Microparticles in Systemic Lupus Erythematosus

Abstract

Objective. To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases.Methods. Using differential centrifugation and high-sensitivity nano-liquid chromatography tandem mass spectrometry, we systematically profiled proteins of microparticles (MPs) from SLE patients (n ‫؍‬ 12), systemic sclerosis (SSc) patients (n ‫؍‬ 6), and rheumatoid arthritis (RA) patients (n ‫؍‬ 6), as well as healthy controls (n ‫؍‬ 12).Results. We identified 531 unique proteins and showed that the differences between healthy controls and patients with SLE with regard to the abundance of 248 proteins were highly statistically significant. Almost half of the proteins that were increased by >2-fold were complement proteins and Ig (increased by 100-4,000 times). MP Ig and complement loads also distinguished SLE from RA and SSc and correlated strongly with clinical SLE severity. Subsets of microtubule proteins, fibronectin, 14-3-3, and desmosomal proteins as well as ficolin 2 and galectin 3 binding protein were also highly increased. In SLE MPs, levels of cytoskeletal, mitochondrial, and organelle proteins, including lysosome-associated membrane protein 1 and transforming growth factor ␤1, were decreased.Conclusion. The data show that SLE patients have increased numbers of MPs that are heavily tagged for removal and fewer MPs with normal protein composition. SLE MPs are unique and specific proteins that represent novel leads for our understanding of SLE and for the development of new treatments of the disease.

Proteomic analysis of human plasma and peripheral blood mononuclear cells in Systemic Lupus Erythematosus patients

“…Epidemiological studies suggest that elevated plasma fibrinogen levels are associated with an increased risk of cardiovascular disorders, such as stroke, ischemic heart disease and other throm- Conversely, Watanabe et al [103] observed that serum levels of L-ficolin in patients with SLE were significantly lower when compared with those in healthy subjects. Our results are in agreement with Østergaard et al [104] because they showed an increase in plasma levels of ficolin-2 in SLE patients compared to healthy subjects.…”

Altered profile of circulating microparticles in rheumatoid arthritis patients

“…Recent studies analysing the MP proteome support this idea [43]. Accordingly, differential 'MP signature' was found in synovial fluid from RA patients compared with other arthritidies [44].…”

The effect of cell death in the initiation of lupus nephritis

“…In addition, endothelial bound nucleosomes and C1q are targets for autoantibodies and lead to activation of complement [52]. Endothelial cells are activated during inflammatory processes and may release microparticles containing chromatin fragments that bind anti-dsDNA antibodies [53,54]. Staining kidney sections of New Zealand black/white F1 (NZB/W F1) mice with antiMeca32 and endoglin (CD105) antibodies revealed that IC deposits in the mesangial matrix contained Meca32 and endoglin (Fig.…”