Background We recently observed that 45% of patients with RA in clinical remission had ultrasound-defined synovitis (grade 2 or higher synovial hypertrophy (SH) and power Doppler signal). These patients had greater disease activity, less use of low-dose corticosteroids and higher serum levels of bFGF (Ramirez J, et al. Arthritis Res Ther 2014).
Objectives We here describe the pathological findings and their correlation with sonographic features in a subset of patients with synovial biopsy.
Methods At baseline, we obtained 6-8 ultrasound-guided synovial biopsies of all RA patients in remission and Power Doppler signal who signed informed consent. CD3 (T lymphocytes), CD20 (B lymphocytes), CD68 (macrophages), CD117 (mast cells) and bFGF were quantified by Immunoperoxidase staining and Digital Image Analysis (Olympus). The number of vessels/mm2 was quantified on hematoxylin-eosin stained sections. Serum bFGF was analysed by ELISA (RayBiotech). We performed ultrasound scans of both knees and hands (wrists, metacarpophalangeal [MCP], proximal interphalangeal [PIP] flexor and extensor tendons of the hand) (Acuson Antares®, Siemens AG, Erlangen, Germany) with a 8-12 MHz linear probe. We independently quantified SH and power Doppler signal (grade 0 -3) and obtained a global ultrasound score for each patient as grade of synovial hypertrophy + grade of power Doppler signal in each assessed joint.
Results We included 19 patients, 13 females, aged 52.1 (8.9) years, with disease duration of 77 (47.4) months (Mean (SD)). 57.9% and 89.5% of patients were positive for rheumatoid factor and anti-citrulline antibodies, respectively; 84.2% were treated with ≥1 DMARD and 57.9% were on biological therapy. On ultrasound, 78.9% of patients had grade 2 or higher SH, and 68.4% ultrasound-defined active synovitis (SH≥2 + power Doppler signal) in at least 1 joint.
A significant positive correlation between the individual global ultrasound score and the density of CD3 + T cells (p=0.02) and CD20+ B cells (p=0.002) was found, and a non- significant trend with CD117+ mast cells density (p=0.09). bFGF expression and number of vessels per area in synovial tissue were non-significantly higher (p=0.11 and p=0.14, respectively) in patients with ultrasound-defined active synovitis. A significant correlation between bFGF expression in synovial tissue and serum bFGF levels (p=0.045) was also found.
Conclusions We found a significant correlation between the grade of infiltration of synovium by T and B lymphocytes and global ultrasound score and between bFGF expression in synovial tissue and serum, suggesting that ultrasound-defined synovitis in patients in clinical remission have a histological and biological correlate. Therefore, bFGF could be a biomarker of subclinical synovitis in RA patients in remission.
Disclosure of Interest : None declared
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