Background Type 1 Interferon (IFN) expression has been shown to correlate with disease severity in systemic lupus erythematosus (SLE) patients¹ and anti-IFN biologics are being evaluated in a clinical setting.² The 4-gene IFN response signature of IFI27, IFI44, IFI44L and RSAD2² is frequently used to determine IFN expression. However, numerous studies have reported on the use of different gene signatures.^{3, 4, 5} The impact of using different IFN gene signatures to stratify SLE patients is unclear.

Objectives The present study compares the relative performance of 4 IFN gene signatures in a cohort of 687 participants with self-reported SLE.

Methods 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.

Results 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 RSAD2² identified 36.5% of the participants as IFN high. Three other literature reported IFN signatures^{3, 4, 5} provided similar classification results with participants being assigned to the same IFN sub-group over 90% of the time, and nearly identical patient distributions.

Conclusions 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.

References [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 & 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.

Disclosure of Interest 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