Introduction
Rheumatoid arthritis (RA) is a systemic autoimmune disease that involves activation of inflammatory cells, synovial hyperplasia, and destruction of cartilage and bone(1). In recent years, anti-citrullinated protein/peptide antibodies (ACPAs) have been used as biomarkers in the diagnosis of RA, and to predict clinical outcomes(2-4). Based on the presence or absence of ACPA, RA can be classified into two subtypes as ACPA-positive (ACPA+) or ACPA-negative (ACPA-). It has been reported that ACPAs are detectable years before the onset of arthritis, and they are strong predictors of progression to classic RA in patients with undifferentiated arthritis(5, 6). Moreover, ACPAs are associated with RA severity. RA patients with ACPAs exhibit more severe radiographic damage than those without ACPAs(7-10). Many studies have suggested that ACPAs play a pathophysiologic role in RA(11). In recent years, a number of candidate genes have been shown to be differentially associated with susceptibility in ACPA+ and ACPA-RA(12-14). With the advent of next-generation sequencing technologies such as RNA sequencing, more comprehensive and accurate transcriptome analysis has become feasible and affordable. In RNA sequencing, short fragments of complementary DNA (cDNA) are sequenced (‘reads’) then mapped onto the reference genome. RNA sequencing facilitates both the identification of differentially expressed genes and precise quantitative determination of exon and isoform (alternative splicing) expression, along with the characterisation of transcription initiation sites and new splicing variants(15, 16).
In the present study, comprehensive transcriptome analysis of PBMCs from ACPA+ and ACPA- RA patients was performed to identify novel candidate gene signatures that might be involved in the pathogenesis of different subsets of disease.