ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2091

Plasma Microparticle Protein Features Distinctively Classify Systemic Lupus Erythematosus and Systemic Sclerosis and Their Clinical Phenotype

Ole Østergaard1, Christoffer T. Nielsen2, Line V. Iversen3, Anders A. Bengtsson4, Søren Jacobsen5 and Niels H. H. Heegaard6, 1Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institute, Copenhagen S, Denmark, 2Infectious Diseases and Rheumatology, University Hospital Rigshospitalet, Copenhagen, Denmark, 3Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark, 4Department of Clinical Sciences, Section of Rheumatology, Lund University, Lund, Sweden, 5Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, 6Department of Clinical Biochemistry & Pharmacology, Odense University Hospital, Odense C, Denmark

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Title: Genetics, Genomics and Proteomics

Session Type: Abstract Submissions (ACR)

Background/Purpose

Plasma microparticles (MPs) comprise a heterogenous population of submicron membraneous vesicles shed from the cell-surface both constitutively and as a consequence of pathological processes. We isolate MPs from well-characterized patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and from healthy controls (HCs) for thorough comparative analysis at the proteome levels. 

Methods

MPs were isolated from 1 mL platelet poor citrate plasma by repeated ultracentrifugation using a standard protocol (1) before in-solution digestion with trypsin followed by analysis by tandem mass spectrometry for protein identification and quantification (2). In total, MPs from 45 SLE patients and 37 SSc patients (all fulfilled the relevant American College of Rheumatology Disease Criteria) were analyzed and compared to MPs from 35 age- and sex-matched healthy controls.  

Results

More than 1000 proteins were identified from each group. Univariate statistics, hierarchical clustering, and principal component analysis were applied to analyze the protein intensities to search for disease classifiers. Samples from SLE patients showed increased levels of complement factors, immunoglobulin, galectin-3-binding protein, CD5-like protein and decreased levels of organellar and membrane associated proteins. In addition, proteins intensities from C1q, G3BP and 14-3-3 showed correlation with disease activity. SSc samples showed increased levels of complement factors and extracellular matrix proteins (fibulin, fibronectin) and decreased levels of tropomyosin-1 and various mitochondrial proteins. Principal component analysis on the centered dataset could differentiate the SLE samples from the NOR and SSc samples.

Conclusion

In-depth proteomic characterization of plasma MPs in SLE and SSc supports their putative role in disease pathology, immune regulation and as biomarkers.

(1)    Nielsen, C. T.; Østergaard, O.; Johnsen, C.; Jacobsen, S.; Heegaard, N. H. Distinct features of circulating microparticles and their relationship to clinical manifestations in systemic lupus erythematosus. Arthritis Rheum. 2011. 2011 Oct;63(10):3067-77

(2)    Østergaard O, Nielsen CT, Iversen LV, Jacobsen S, Tanassi JT, Heegaard NH. Quantitative proteome profiling of normal human circulating microparticles. J Proteome Res. 2012 Apr 6;11(4):2154-63

Disclosure:

O. Østergaard,
None;

C. T. Nielsen,
None;

L. V. Iversen,
None;

A. A. Bengtsson,
None;

S. Jacobsen,
None;

N. H. H. Heegaard,
None.

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