Circular RNA expression profiles and identification of hsa_circ_0028381 as a potential biomarker of anti-neutrophil cytoplasmic antibody-associated vasculitis.

ABSTRACT

OBJECTIVES: Accumulating evidence indicates the role of dysregulated circRNAs in autoimmune diseases. In this study, we investigated their role in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) by analysing the expression profiles of circRNA in plasma of AAV patients and exploring their potential as biomarkers of AAV. METHODS: RNA-sequencing (RNA-seq) was performed to identify the plasma circRNA and mRNA expression profiles from five AAV patients and five healthy controls (HCs). Quantitative reverse-transcription (qRT)-PCR confirmed that hsa_circ_0028381 was confirmed to be significantly upregulated in a validation cohort of 51 AAV patients and 30 HCs and was further verified in other connective tissue diseases (CTDs). The diagnostic value of hsa_circ_0028381 was assessed by receiver operating characteristic (ROC) curve analysis. RESULTS: RNA expression profiles revealed aberrant expression of 143 circRNAs (62 upregulated and 81 downregulated) and 304 mRNAs (151 upregulated and 153 downregulated) in AAV patients compared to HCs. qRT-PCR verification suggested that hsa_circ_0028381 levels were significantly increased in plasma from AAV patients compared to those in HCs and other CTDs. ROC curve analysis showed has_circ_0028381 had good diagnostic value for distinguishing AAV patients from controls (HCs and other CTDs) with an area under the curve (AUC) of 0.81. In addition, hsa_circ_0028381 was associated with renal involvement. Most importantly, increased baseline levels of hsa_circ_0028381 had predictive value for progression to end-stage renal disease (ESRD). CONCLUSIONS: RNA-seq revealed that circRNAs are aberrantly expressed in the plasma of AAV patients. Hsa_circ_0028381 was implicated as a potential biomarker for AAV diagnosis and renal prognosis.