Background The synovial cellular infiltrate in RA has for some time been recognised to organise into lymphocytic aggregates with a number observations suggesting they are immunologically competent and can support chronic inflammation. However, their clinical significance has been controversial with conflicting publications reporting diverse associations with disease outcome.
Objectives The aim of this study was to examine in a cohort of therapy naïve, early RA patients whether baseline synovial pathotype: i)associated with specific clinical phenotypes, ii)predicted response to DMARD therapy, and iii)predicted joint damage progression
Methods 135 DMARD-naïve early RA patients were recruited as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust. Following pre-treatment synovial biopsy clinical data was collected at baseline and 12 months. Following immunohistochemical staining the degree of synovial infiltration by CD20+B cells, CD3+T cells, CD68+macrophages and CD138+plasma cells was determined. Patients were then categorised into synovial pathotypes: lymphoid, myeloid or fibroid according to the degree of immune cell infiltration. Samples also underwent nanostring analysis of 238 genes. Significant differences in clinical parameters at baseline and progression in radiographic damage at 12 months between synovial pathotypes was determined.
Results At baseline a lymphoid pathotype significantly associated with ACPA+ve (0.017) and highly active disease (DAS28, CRP, ESR and swollen joint count, p<0.01). Furthermore a significantly higher number of patients with a baseline lymphoid pathotype (vs myeloid/fibroid) developed radiographic progression (9/26 vs 5/53, p=0.026). A cohort of 79 genes were identifed from the nanostring analysis that were differentially upregulated in patients with joint damage progression. Logistic regression analysis was used to develop a clinical model for predicting radiographic progression (final model ESR, RF and ACPA) with an AUC of 0.86. Integration of synovial gene expression profiles into the clinical model improved the AUC to 0.96.
Conclusions The demonstration in this early RA cohort of a significant association between a lymphoid pathotype and a severe clinical phenotype/sero positivity for ACPA supports a direct role for synovial lymphoid structures in disease pathogenesis. Furthermore patients with a lymphoid pathotype were significantly more likely to develop radiographic damage. Integration of synovial gene expression profiles into a clinical model of radiographic progression enhanced performance. This data strongly supports a role for integration of synovial biomarkers into clinical prediction models of radiographic progression in early RA with critical implications for future patient stratification.
Disclosure of Interest None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.