Document resource
Objectives Systemic lupus erythematosus (SLE) is characterised by broad immune dysregulation in which type I interferon (IFN) pathways are frequently enhanced in active disease, but it is not clear whether this signature remains during remission. In this study, we compared IFN and related immune signatures between patients with SLE in sustained remission and healthy control subjects (HC).Methods Serum samples from patients with SLE were analysed using the NUcleic acid Linked Immuno-Sandwich Assay (NULISA) Inflammation Panel 250 (Alamar). The panel used enables quantification of 250 inflammation proteins simultaneously at very low concentrations. Remission was defined as; 1. Clinical SLEDAI-2K = 0, off immunosuppression and glucocorticoids (Hydroxychloroquine alone permitted) for a minimum of two years at the time of sample collection (n=49) and compared with HC (n=11) were recruited for analysis. Data were analysed after normalization and quality control. Statistical significance was defined as p<0.05 following a correction for false discovery rate (FDR) of 5%.Results SLE patients in persistent remission had significantly different expression of multiple markers compared with HC ( figure 1). Broadly, this involves several immune pathways1. IFN centred, checkpoint and inflammatory amplification pathways. This was characterised by upregulation of IFN alpha (IFNA1, IFNA13) and gamma (IFNG), tetherin (BST2), LGALS9, IL6, and CD70 with downregulation of the IFN inhibitory receptor (CD200R1).2. Neutrophil–myeloid/complement axis (granulopoiesis, NET-linked injury, acute phase response) pathways. This was characterised by increased CSF3, CXCL8, MMP8, PTX3, S100A9, TNFSF14, C1QA, CCL7 with associated reduction in macrophage migration inhibitory factor (MIF).3. Endothelial activation and angiogenesis activation. Demonstrated by an increase in VEGFD, EGF and GFAP with reduced PDGFA/B, THBS2, TIMP1, AGER and CCL26.4. T cell homeostasis, IL2 pathway & co-stimulation/antigen presentation pathways. This is supported by increased CD70 and IFNG with reductions in CD3E, TNFSF9 and HLA-DR.5. B cell survival & stromal/epithelial repair and morphogen programme pathways. Typified by decreased TNFSF13 (APRIL), TNFSF12 (TWEAK), Bone Morphogenetic Protein 7 (BMP7), Wnt Family Member 16 (WNT16), KIT Ligand (KITLG), IL20, IL17B/C and IL36A/B.Abstract PO:02:062 Figure 1Conclusions Patients in sustained remission present with a ‘molecular residual disease’ . A composite multi-analyte signature could refine risk stratification and guide treatment de-escalation.