Using comprehensive transcriptome analysis to reveal the landscape of pathobiology in early rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects the joints resulting in progressive pain, stiffness and swelling. Due to the limited response to treatment and heterogeneous nature of the condition, there is a current drive to identify patient subgroups with distinct mechanisms of disease in order to develop therapies that are most effective for that particular group.MethodsA total of 87 disease tissue (synovium) and 67 blood biopsies were obtained from treatment-naïve early-RA patients, together with clinical and demographic data, as part of the Pathobiology of Early Arthritis Cohort (PEAC). RNA-sequencing was performed on each biopsy in order to determine differential expression between patient groups.ResultsWe identified transcriptional subgroups in synovium linked to three distinct pathotypes: fibroblastic pauci-immune pathotype, macrophage-rich diffuse-myeloid pathotype, and a lympho-myeloid pathotype. In order to illustrate variances between these groups, we developed an interactive 3D volcano plot to highlight the three-way differences in gene expression. We also created a data exploration website with the ability to correlate specific genes or gene modules with histological, clinical, and radiographic parameters thereby allowing the wider research community to examine the results further.ConclusionBy comparing gene expression in both synovium and blood we identified markers that are suggestive of divergent pathogenic pathways and could predict disease progression or response to treatment bringing us closer to a stratified medicine model.
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