Background/Purpose: IFN signatures are known to play an important role in the pathogenesis of systemic autoimmune diseases such as SLE. Recently, therapeutic agents targeting IFN (JAK inhibitors, anifrolumab (ANI)) have been used to treat these diseases; ANI is an antibody against subunit 1 of the type I IFNα receptor (IFNAR1), and in the TULIP study, it was shown to be more effective in a subgroup of SLE patients with high IFN signatures¹⁾. The IFN signature is evaluated by the combination of the expression levels of various mRNAs induced by IFNs, and if the degree of the IFN signature is evaluated before selecting a treatment, it will be possible to increase the therapeutic effect. However, it is not practical to evaluate gene expression in general clinical practice due to cost.Therefore, in this study, we develop a simple method for estimating IFN signatures from general clinical laboratory test items.

Methods: A total of 36 peripheral blood samples from 21 SLE patients untreated or after 6 months of treatment were analyzed for gene expression using next-generation sequencing. 73 genes were selected as Type-1 IFN-related genes, 94 genes as Type-2 IFN-related genes, and 10 genes as Type-3 IFN-related genes (2, 3), and the IFN signature was evaluated by scoring the sum of the Z-Score of each gene expression as the IFN score. For general laboratory tests, 129 items consisting of urinalysis, blood count, blood biochemical tests, and immunological tests were evaluated. Multiple regression analysis was performed to select the general laboratory tests that best predicted IFN score.

Results: All type 1-3 IFN scores were significantly elevated in SLE patients compared to healthy controls. There was a trend toward a positive correlation between each IFN score and neutrophil count, and a negative correlation with lymphocyte count. The strongest correlation was observed when the neutrophil/lymphocyte ratio (NLR) was calculated and used: the correlation coefficient between Log2NLR (Min.=-0.34, 1st Qu.=1.64, Mean=1.79, 3rd Qu.=2.56, Max.=4.83) and the IFN score was significantly higher in Type 1 IFN (R2=0. 57, P=1.74e-07), Type 2 IFN (R2=0.36, P=1.74e-07) and Type 3 IFN (R2=0.57, P=1.32e-07).

Conclusion: ANI has been shown to be more effective in a subgroup of SLE patients with high IFN signatures.The NLR showed a strong correlation not only with Type 1 IFN, but also with Type 2 and 3 IFN signatures.Since the NLR can be easily calculated in daily clinical practice, it can be used to enable easy estimation of IFN signatures, which may be useful for clinical applications.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/to-develop-a-method-for-estimating-interferon-signatures-in-sle-from-routine-clinical-laboratory-tests/