Unique Protein Signature of Circulating Microparticles in Systemic Lupus Erythematosus

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 65; no. 10; pp. 2680 - 2690
• Main Authors: Østergaard, Ole, Nielsen, Christoffer T., Iversen, Line V., Tanassi, Julia T., Knudsen, Steen, Jacobsen, Søren, Heegaard, Niels H. H.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-10-2013
• Subjects: Adult; Aged; Arthritis, Rheumatoid - metabolism; Autoimmune diseases; Case-Control Studies; Cell-Derived Microparticles - metabolism; Female; Gene Expression Profiling; Humans; Immune system; Lupus; Lupus Erythematosus, Systemic - metabolism; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microtubule Proteins - genetics; Microtubule Proteins - metabolism; Middle Aged; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Proteins; Proteins - genetics; Proteins - metabolism; Scleroderma, Systemic - metabolism
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.38065

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, 14‐3‐3η, 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 β1, 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.