Identification of IFI44L as a new candidate molecular marker for systemic lupus erythematosus.

ABSTRACT

OBJECTIVES: We screened the type I interferon signal pathway factor involved in the pathogenesis of systemic lupus erythematosus (SLE) by whole-genome sequencing in SLE patients and initially analyse their potential functions. METHODS: Use high-throughput sequencing technology to sequence mRNAs on peripheral blood mononuclear cells from SLE patients and healthy controls,and screen out differentially expressed genes related to the type I interferon (IFN) pathway. Quantitative reverse transcription PCR (RT-qPCR) was utilised to verify the expression of the IFI44L gene in SLE patients and healthy controls, and the correlation between its expression level and clinical test indicators of SLE patients were analysed. The receiver operating characteristic (ROC) analyses were conducted to explore the value of IFI44L for SLE diagnosis. Cell counting kit-8 assay and flow cytometry were used to detect the effects of IFI44L on cell proliferation, apoptosis, and cell cycle. RESULTS: A total of 122 genes were significantly up-regulated and 34 genes were significantly down-regulated in the SLE group compared with the healthy control group in this research. The significantly up-regulated IFI44L in SLE patients was verified by RT-qPCR (p<0.01), furthermore, male SLE patients were significantly higher than that in female SLE patients (p<0.05). Moreover, ROC analyses proved IFI44L may have diagnostic value for SLE. Meanwhile, IFI44L expression level was significantly correlated with platelets, mean platelet volume, red blood cell distribution width to platelet ratio, complement component 3, and C-reactive protein (p<0.05). In addition, under the action of high interferon, IFI44L can resist the proapoptotic effect of IFN-α and improve the proliferation activity of cells. CONCLUSIONS: IFI44L may play an important role in SLE pathology through abnormal regulation of the type I interferon signalling pathway.