Molecular portraits of early rheumatoid arthritis identify clinical and treatment response phenotypes

Journal article

There is a current imperative to unravel the hierarchy of molecular pathways that drive the transition of early to established disease in rheumatoid arthritis (RA). Herein, we report a comprehensive RNA sequencing analysis of the molecular pathways that drive early RA progression in the disease tissue (synovium), comparing matched peripheral blood RNA-seq in a large cohort of early treatment-naive patients, namely, the Pathobiology of Early Arthritis Cohort (PEAC). We developed a data exploration website (https://peac.hpc.qmul.ac.uk/) to dissect gene signatures across synovial and blood compartments, integrated with deep phenotypic profiling. We identified transcriptional subgroups in synovium linked to three distinct pathotypes: fibroblastic pauci-immune pathotype, macrophage-rich diffuse-myeloid pathotype, and a lympho-myeloid pathotype characterized by infiltration of lymphocytes and myeloid cells. This is suggestive of divergent pathogenic pathways or activation disease states. Pro-myeloid inflammatory synovial gene signatures correlated with clinical response to initial drug therapy, whereas plasma cell genes identified a poor prognosis subgroup with progressive structural damage.

Authors: Lewis, MJ; Barnes, MR; Blighe, K; Goldmann, K; Rana, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell Reports
• Volume: 28
• Issue: 9
• Pages: 2455-2470
• Publication date: 2019-08-27
• Acceptance date: 2019-07-24
• DOI: 10.1016/j.celrep.2019.07.091
• ISSN: 2211-1247
• Keywords: transcriptomics; rheumatoid arthritis; synovial biopsy; personalised medicine; RNA sequencing; ectopic lymphoid structures; lymphoid neogenesis; Pathobiology of Early Arthritis Cohort study (PEAC)