Background/Purpose: Synovial inflammation is known to play a central role in articular cartilage degradation in rheumatoid arthritis (RA); it could be a passive marker of disease, or the driving force in the onset of early joint damage. In this study we aimed to determine if circulating metalloproteinase-3 (MMP-3) and hyaluronic acid (HA) would outperform CRP as surrogate biomarkers for synovitis detection

Methods: Patients fulfilled 1987 ACR RA classification criteria, had 3-12mth symptom duration, active disease (DAS44>2.4) and were DMARD naïve. In a subset, grey scale (GS) and power Doppler (PD) ultrasound (US) semi-quantitative scores (0-3) were assigned to wrists, MCPs & PIPs 2&3 and MTPs 1-5 bilaterally at baseline¹. For this analysis both counts (joints scoring GS>1, PD>0, simultaneously GS>1 & PD>0) and score totals were created. To reflect burden of synovitis, clinical and US counts and totals were weighted by first multiplying each joint’s score by a weight, determined by its relative area², before summating. Samples were tested for MMP-3 and HA using a novel research use only multiplex platform IMPACT(Immunological Multi-Parameter Chip Technology)(Roche Professional Diagnostics, Germany)³. We calculated bootstrapped confidence intervals(CI) for the differences in the strength of Kendall’s tau-a associations between markers and joint assessments in Stata 13.1.

Results: Data were available for 59 patients: mean age 52.7 (range 19-78); 71% female; 64% RF +ve; median disease duration 1mth. Median (IQR) values for markers were CRP 27mg/L (10, 100); MMP-3 59ng/mL (42, 119); HAμg/mL 37 (20, 70).

None of the associations were particularly strong (Table 1); the strongest were between the weighted clinical joint counts and MMP3 and CRP. Most of the associations with MMP3 were numerically stronger than with CRP, but the differences were neither substantive nor statistically significant.

In patients with normal CRP (<10 mg/L) there appeared to be substantive associations between total GS and MMP-3 (tau-a=0.34) and between total PD and HA (tau-a=0.35); however, sample size was small (n=14).

Table1: Associations between markers of inflammation and clinical and ultrasound measures of synovitis, weighted for joint area (n=59).

Conclusion: This is the first time that weighted joint counts, which account for joint surface area, have been used in the assessment of soluble synovial biomarkers in RA. Neither MMP3 nor HA performed better as surrogate biomarkers of synovitis than CRP when elevated. Further studies are underway to evaluate the clinical utility of MMP3 as a soluble biomarker of subclinical synovitis at CRP levels<10mg/L.

References: 1) Nam J, et al. ARD2014; 73: 75 2) Lansbury J, et al. Am J Med Sci1956; 232: 150 3) Claudon A, et al. Clin Chem2008; 54: 1554.

Funding:Roche Professional Diagnostics provided free of charge access to the IMPACT platform and IMPACT reagents. This work was also supported by grants from ARUK and the NHIR.