Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

Molecular Portraits of Early Rheumatoid Arthritis Identify Clinical and Treatment Response Phenotypes


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 ( 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.

Type Journal
ISBN 2211-1247 (Electronic)
Authors Lewis, M. J.; Barnes, M. R.; Blighe, K.; Goldmann, K.; Rana, S.; Hackney, J. A.; Ramamoorthi, N.; John, C. R.; Watson, D. S.; Kummerfeld, S. K.; Hands, R.; Riahi, S.; Rocher-Ros, V.; Rivellese, F.; Humby, F.; Kelly, S.; Bombardieri, M.; Ng, N.; DiCicco, M.; van der Heijde, D.; Landewe, R.; van der Helm-van Mil, A.; Cauli, A.; McInnes, I. B.; Buckley, C. D.; Choy, E.; Taylor, P. C.; Townsend, M. J.; Pitzalis, C.
Responsible Garvan Author A/Prof Sarah Kummerfeld
Publisher Name Cell Reports
Published Date 2019-08-29
Published Volume 28
Published Issue 9
Published Pages 2455-2470 e5
Status Published in-print
DOI 10.1016/j.celrep.2019.07.091
URL link to publisher's version