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THU0315 Serum Protein Pattern of Systemic Lupus Erythematosus Using Proximity Extension Immunoassay
  1. A. Petrackova1,
  2. A. Smrzova2,
  3. M. Schubertova2,
  4. P. Schneiderova1,
  5. T. Dyskova1,
  6. M. Skacelova2,
  7. F. Mrazek1,
  8. P. Horák2,
  9. E. Kriegova1
  1. 1Dept. of Immunology, Palacky University Olomouc
  2. 2Dept. of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, University Hospital, Olomouc, Czech Republic

Abstract

Background Systemic lupus erythematosus (SLE) is a severe autoimmune connective tissue disorder. Current knowledge about the serum protein pattern associated with SLE is still limited.

Objectives To identify SLE-associated serum protein signature using innovative multiplex Proximity Extension ImmunoAssay (PEA).

Methods We investigated the serum levels of 92 inflammation-related proteins in 76 Czech patients with SLE and 24 age-matched healthy control subjects (C) using a highly sensitive multiplex PEA (Proseek Multiplex, Olink Bioscience, Sweden). Statistical tests (Student t-test, Benjamini-Hochberg correction, Principal component analysis (PCA)) were performed using GenEx (Sweden), P-value <0.05 was considered as significant.

Results When comparing SLE to control subjects, serum levels of 30 proteins were deregulated (P<0.05 after multiple comparisons). PCA revealed three proteins distinguishing SLE and C: sirtuin 2 (SIRT2; SLE vs C fold change: 2.1, P=0.000005), interleukin 18 (IL18; 1.5, P=0.00002) and sulfotransferase 1A1 (ST1A1; 2.2, P=0.00007). Interestingly, SIRT2 and ST1A1 were not reported in SLE yet; from neuroinflammation there is evidence that SIRT2 regulates NFκB signalling and Toll-like receptors, ST1A1 contributes to resistance to anti-inflammatory treatment. Among other highly-deregulated proteins, we observed elevation of many inflammatory mediators (IL-18R1, CCL4, CSF1, SLAMF1, CD40 and TNFRSF9), and also of Caspase 8, a metalloprotease STAMBP and Axin-1, a modulator of Wnt-signalling pathway (P<0.0005) in SLE. Subanalysis of protein pattern in patient phenotypes is ongoing.

Conclusions This first study using PEA identified SLE-associated serum signature, with many of novel proteins not yet reported in SLE. Their exact function and suitability as biomarkers in SLE deserves further investigation.

Acknowledgement MZ CR VES15–28659A, IGA_UP_2016_11

Disclosure of Interest None declared

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