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