Background/Purpose: Gene expression studies have previously demonstrated increased Type I interferon α (IFN) inducible genes in peripheral blood mononuclear cells of systemic lupus erythematosus (SLE) patients as compared to controls. Prior studies also showed increased IFNα gene expression is associated with markers of disease activity, both by disease activity scores and serological markers (Kennedy et al, 2015 and Kirou et al 2005). Despite the success of large phase II trials of anti-IFN therapies in patients with SLE, phase III trials were reportedly negative. Identifying the optimal biomarker in order to target the appropriate population of SLE patients to receive anti-IFN therapy remains elusive and a critical goal. Rather than using IFNα inducible genes as biomarkers, we investigated IFNα subtype expression in SLE patients versus healthy controls. We also evaluated associations of IFNα subtype expression in SLE patients with disease-related characteristics and clinical phenotype.

Methods: Patients were recruited from Beth Israel Deaconess Medical Center and the protocol was approved by our institution’s IRB. We obtained serum samples from 26 patients and 4 controls. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of interferon α subtypes (1, 2, 4, 5, 6, 7, 8, 10, 14, 16, 17, 21) and β-actin mRNA were done using the Inexsia/Amplikine platform (PBL InterferonSource, Piscataway, NJ).  For each mRNA/cDNA in the sample, the fluorescence threshold cycle (Ct) during the amplification reaction was identified. The Dct was then calculated for each interferon α subtype mRNA by subtracting its Ct from the β-actin Ct (Dct _{interferon α subtype}=Ct_actin-Ct_{interferon α subtype}).  Statistical analyses were done using SPSS. Between group differences were analyzed with independent samples t-test. Multiple linear regression analyses were conducted to evaluate for independent associations between IFNα expression, SLEDAI, autoantibodies, markers of disease activity and clinical phenotypes. Follow up correlational analyses were done using Pearson’s correlation.

Results: Analyses revealed that Type I IFN α2 mRNA expression in patients’ peripheral blood mononuclear cells was elevated as compared to controls (p = 0.02, t= -2.65). No other subtypes demonstrated between group differences. Type I IFN α2 mRNA expression in patients trended towards correlating with disease activity as measured by SLEDAI scores (p =0.07, F= 4.2). There was also a trend found for a correlation between IFN α2 expression and lupus nephritis (R=.48, p=.067). No serological markers of disease activity or autoantibodies were significantly associated with IFN α2 expression.

Conclusion: Prior studies and clinical trials investigating IFNα in SLE used surrogate markers to deduce IFNα production. We propose that direct measurement of IFNα production at the mRNA level is feasible and can potentially be used as a biomarker for guiding anti-IFNα therapy in patients with SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/measurement-of-type-i-ifn%ce%b1-production-at-the-mrna-level-and-its-potential-use-as-a-biomarker-in-systemic-lupus-erythematosus/