Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
We recently demonstrated that 45.4% of patients with RA in clinical remission have ultrasound (US)-defined active synovitis (synovial hypertrophy (HS) grade 2 or higher and Power Doppler [PD] signal) (Ramírez J et al, arthritis Research and Therapy 2014). Here we analysed the histological correlate of US-defined active synovitis in a subset of patients in whom synovial biopsy was performed.
Methods
By protocol, we obtained at baseline 6-8 ultrasound-guided synovial biopsies of all patients with (PD) signal who had signed the informed consent. Immunohistochemical staining was performed by the the peroxidase technique for the following antibodies: CD3 (T lymphocytes), CD20 (B lymphocytes), CD31 (vessels), CD68 (macrophages), CD117 (mast cells), Hsp47 (Fibroblast-like synoviocytes)(Izquierdo E et al, Arthritis Rheum 2011) and basic FGF. Quantifications were perfomed by Digital Image Analysis (Olympus). Serum bFGF was analyzed by Quantibody® Human Array (RayBiotech). US scans of both knees and hands (wrists, metacarpophalangeal [MCP], proximal interphalangeal [PIP]) were performed by an experienced rheumatologist using a high sensitivity equipment (Acuson Antares®, Siemens AG, Erlangen, Germany) with a 8-12 MHz linear probe. We quantified the presence of synovial hypertrophy (grades 0-3) and (PD) signal (grades 0-3) in all patients.
Results
We have included 24 patients with synovial biopsy. Regarding US assessment, 100% of patients had PD signal (by protocol), 79.2 % had Synovial HS grade 2 or higher, while 70.8% met criteria for US-defined active synovitis (HS> 2 + [PD] signal) at least in one joint .
The number of B cells (CD20+)/mm2 (p=0.017) and immunostained fractional area of Hsp47+ fibroblasts (p=0.035) in synovial tissue were significantly higher in patients with US-defined active synovitis. Furthermore, these patients had a non-significant greater number of CD31+ vessels per area (p=0.061).
The expression of bFGF in the synovial tissue showed a strong trend to correlation with its concentration in serum (p = 0.064). We also analyzed the expression of bFGF in synovial tissue in two control populations (19 patients with active RA and 8 healthy controls). bFGF expression was higher in patients with active rheumatoid arthritis (DAS28>3.2) than in patients in remission. Furthermore, bFGF expression was lower in healthy controls than in patients in remission. Thereby, these preliminary results point to bFGF expression is parallel to disease activity.
Moreover, a significant correlation of global US score of each patient with the number of T cells (CD3+)/mm2 (p=0.010) and B cells (CD20+)/mm2 (p=0.001), and a strong trend to significance in mast cells CD117+ (p=0.064) were found.
Conclusion
These preliminary results support that US-defined active synovitis has a histopathological substrate which is associated with fibroblasts and B cells. Also, the grade of infiltration of the synovium by T and B lymphocytes is associated with the US global score of the patient. Finally, correlation between synovial tissue expression and serum levels of bFGF, a mainly fibroblast-derived factor, point
Disclosure:
J. Ramirez,
None;
V. Ruiz-Esquide,
None;
R. Celis,
None;
A. Usategui,
None;
R. Faré,
None;
A. Cuervo,
None;
S. Cabrera-Villalba,
None;
M. V. Hernández,
None;
J. Inciarte-Mundo,
None;
J. L. Pablos,
None;
R. Sanmarti,
None;
J. D. Cañete,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/histopathological-correlation-of-ultrasound-defined-active-synovitis-in-patients-with-rheumatoid-arthritis-in-clinical-remission-preliminary-results/