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.