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SLE Plasma Profiling Identifies Unique Signatures of Lupus Nephritis and Discoid Lupus

Author

Smith MA1, Henault J1, Karnell JL1, Parker ML1, Riggs JM1, Sinibaldi D1, Taylor DK1, Ettinger R1, Grant EP1, Sanjuan MA1, Kolbeck R1, Petri MA2, Casey KA3,4. Sci Rep. 2019 Oct 8;9(1):14433. doi: 10.1038/s41598-019-50231-y.

Author Information

1 AstraZeneca, Gaithersburg, MD, USA.

2 Johns Hopkins University School of Medicine, Baltimore, MD, USA. kerry.casey@alleninstitute.org.

3 AstraZeneca, Gaithersburg, MD, USA. mpetri@jhmi.edu.

4 Allen Institute for Immunology, 615 Westlake Ave N, Seattle, WA, 98109, USA. mpetri@jhmi.edu.

Abstract

Systemic lupus erythematosus (SLE) impacts multiple organ systems, although the causes of many individual SLE pathologies are poorly understood. This study was designed to elucidate organ-specific inflammation by identifying proteins that correlate with SLE organ involvement and to evaluate established biomarkers of disease activity across a diverse patient cohort. Plasma proteins and autoantibodies were measured across seven SLE manifestations. Comparative analyses between pathologies and correlation with the SLE Disease Activity Index (SLEDAI) were used to identify proteins associated with organ-specific and composite disease activity. Established biomarkers of composite disease activity, SLE-associated antibodies, type I interferon (IFN), and complement C3, correlated with composite SLEDAI, but did not significantly associate with many individual SLE pathologies. Two clusters of proteins were associated with renal disease in lupus nephritis samples. One cluster included markers of infiltrating leukocytes and the second cluster included markers of tissue remodelling. In patients with discoid lupus, a distinct signature consisting of elevated immunoglobulin A autoantibodies and interleukin-23 was observed. Our findings indicate that proteins from blood samples can be used to identify protein signatures that are distinct from established SLE biomarkers and SLEDAI and could be used to conveniently monitor multiple inflammatory pathways present in different organ systems.