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42 Gene expression profile from 1,760 sle patients reveals novel complex interferon responsive gene networks

Background and aims RNA profiling was performed on 1760 SLE patients from two, large Phase III clinical trials, ILLUMINATE-1 and −2. SLE was compared to both healthy controls and other autoimmune diseases, including rheumatoid arthritis, psoriasis and psoriatic arthritis. The goals of this study were to characterise gene expression networks in SLE using these large cohorts, and to compare gene expression phenotypes in SLE to healthy controls and other autoimmune diseases. Methods Blood was collected at baseline and RNA was interrogated on all samples using Affymetrix HTA 2.0 microarrays and on select SLE samples using NanoString nCounterTM. Complete demographics, serum IgG anti-dsDNA antibodies, and complement were measured in SLE. Analyses of gene expression and gene pathways were performed. Results Baseline elevation of interferon responsive genes (IRG) was detected in SLE and associated with younger age, elevated anti-dsDNA antibodies, elevated SLEDAI and decreased levels of C3. Significant differences in SLEDAI organ domain involvement between IRG-positive and IRG-negative groups were observed. Elevated expression of IRG, genes involved with B cell and plasma cell biology, and with cell cycling and signalling were detected in SLE. A bimodal expression pattern of IRG was unique to SLE. Substantial heterogeneity of expression of IRG and complex relationships in interferon (IFN) gene networks were observed. Conclusions There was substantial heterogeneity of gene expression in IFN gene networks when examining individual IFN genes and complex relationships were observed among IFN gene networks. Low IFI27 was identified as a novel subtype of IFN signature in SLE.