Background/Purpose:   Mast cells (MCs) are immune cells present in the synovial membrane and implicated in the pathogenesis of Rheumatoid Arthritis, although their exact contribution to disease development and progression is still unclear. In particular, their presence in synovia has never been evaluated in correlation with longitudinal disease parameters. Aim of this study was to analyse mast cells in the synovia of early RA patients and their correlation with disease outcomes.                                                                                          

Methods:   99 DMARD-naive patients with early (<12 months) RA (n=99) fulfilling the 2010 ACR/EULAR classification criteria were recruited as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust. Sections of paraffin embedded synovial tissue obtained by ultrasound-guided synovial biopsy were stained for CD117+ by immunohistochemistry to calculate the density of CD117+ MCs. Patients were stratified according to MC numbers and clinical parameters at baseline and 12 months follow-up were evaluated.  

Results:   At baseline, high synovial MC counts significantly associated with ACPA and RF positivity (p=0.029 and 0.013, respectively) and higher disease activity (DAS28 p=0.003). Accordingly, the density of synovial MCs at baseline correlated with DAS-28 (rS=0.308, p=0.002), ESR (rS=0.273, p=0.007), CRP (rS=0.217, p=0.033), and swollen joint count (rS=0.308, p=0.002). At 12 months follow-up, patients with high baseline MC counts showed a higher prevalence of radiographic progression (9/26 vs 3/26 vs 1/27 in high, medium and low MC counts, p=0.007, n=79), with no differences in terms of treatment and response to therapy. Among baseline characteristics, only age and MC counts showed a statistically significant difference in progressors Vs non-progressors (Table 1).  

Conclusion:   We show a significant association between synovial mast cells and a severe clinical phenotype and seropositivity for ACPA and RF in a DMARD-naive early RA cohort. Furthermore, patients with high mast cell counts were significantly more likely to develop radiographic damage at 12 months. Interestingly, several baseline parameters, potentially associated with a higher risk of radiographic progression (e.g. antibody positivity, disease activity), were not different in progressors Vs non-progressors, except for age, while mast cell numbers were significantly higher in progressors. Although additional studies are warranted to confirm the association and, possibly, the direct contribution of mast cells to radiographic progression, our work suggests that the analysis of synovial mast cell could be used as a prognostic biomarker for patient stratification in RA. Table 1. Baseline characteristics in radiographic progressors Vs non-progressors