SAT0041 Comparison of different type 1 ifn signatures demonstrates concordance in a real world, home monitored systemic lupus erythematosus cohort
Authors: M. Abedi, F. Flores, P. Naranatt, J. Spangler, L. Pan, R. Terbrueggen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Type 1 Interferon (IFN) expression has been shown to correlate with disease severity in systemic lupus erythematosus (SLE) patients<sup>1</sup> and anti-IFN biologics are being evaluated in a clinical setting.<sup>2</sup> The 4-gene IFN response signature of IFI27, IFI44, IFI44L and RSAD2<sup>2</sup> is frequently used to determine IFN expression. However, numerous studies have reported on the use of different gene signatures.<sup>3, 4, 5</sup> The impact of using different IFN gene signatures to stratify SLE patients is unclear. <h3>Objectives</h3> The present study compares the relative performance of 4 IFN gene signatures in a cohort of 687 participants with self-reported SLE. <h3>Methods</h3> A centralised site, IRB-approved, SLE cohort was recruited using social media. Qualified participants with self-reported SLE were consented electronically and asked to provide medical record review consent, complete an online questionnaire regarding their disease as well as provide 3 fingerstick blood samples over approximately a 6 week period. Blood samples from 687 participants were tested using a multi-modular gene expression assay containing 11 IFN response genes (primarily from the IFN-α response pathway). Normalised gene expression values were calculated, and the resulting data analysed to determine concordance between IFN gene signatures. <h3>Results</h3> 10 of the 11 IFN response genes were highly correlated with one another (ρ ≥0.80). The 4-gene signature of IFI27, IFI44, IFI44L, and RSAD2<sup>2</sup> identified 36.5% of the participants as IFN high. Three other literature reported IFN signatures<sup>3, 4, 5</sup> provided similar classification results with participants being assigned to the same IFN sub-group over 90% of the time, and nearly identical patient distributions. <h3>Conclusions</h3> The study demonstrated that commonly used IFN gene signatures provide similar IFN subtyping to the 90th percentile. The use of social media to engage patients directly along with self-collection of blood samples provides new opportunity for testing clinical study participants and potentially patients without requiring an office visit. <h3>References</h3> [1] Dall'Era M, et al. Type I interferon correlates with serological and clinical manifestations of SLE. Annals of the Rheumatic Diseases2005;64(12):1692–1697. [2] Furie R, et al. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol2017;69(2): 376–386. [3] Niewold TB, et al. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun2007;8(6):492–502. [4] Kirou KA, et al. Activation of the Interferon-alpha Pathway Identifies a Subgroup of Systemic Lupus Erythematosus Patients with Distinct Serologic Features and Active Disease. Arthritis &amp; Rheumatism2005;52(5):1491–1503. [5] Westra HJ, et al. Systematic identification of trans-eQTLs as putative drivers of known disease associations. Nat Genet2013;45(10):1238–1243. <h3>Disclosure of Interest</h3> M. Abedi Shareholder of: DxTerity, Employee of: DxTerity, F. Flores Employee of: DxTerity, P. Naranatt Employee of: DxTerity, J. Spangler Employee of: DxTerity, L. Pan Employee of: DxTerity, R. Terbrueggen Shareholder of: DxTerity, Employee of: DxTerity