Date: Monday, November 6, 2017
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Mast cells (MCs) are immune cells infiltrating the synovial membrane and implicated in the pathogenesis of Rheumatoid Arthritis, but their strict contribution to disease development and progression is still unclear. We have previously shown an association between synovial MCs and disease severity in early RA patients. Aim of this study was to analyse the presence of MCs in the synovia of RA patients at baseline and 6 months after treatment with synthetic DMARDs in relationship with disease parameters and response to treatment.
Methods: DMARD-naïve patients with early (<12 months) RA (n=20) fulfilling the 2010 ACR/EULAR criteria were recruited as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust. Synovial tissue was obtained by ultrasound-guided synovial biopsy at baseline and 6 months after treatment with synthetic DMARDs. Sequentially cut sections were stained by IHC for CD117+ MCs and immune cells (CD20+ B cells, CD3+ T cells, CD68+ macrophages and CD138+ plasma cells). Patients were classified according to the presence or absence of MCs, and MC density (n/mm2) was calculated by automated cell counting (cellSens, Olympus). Upon SQ scoring (0-4), sections were stratified into synovial pathotypes according to the degree of immune cell infiltration: (i) Lymphoid- grade 2/3 B cell aggregates, CD20≥ 2 and/or CD138>2 ii) Myeloid- CD68 SL≥ 2, CD20≤1 and/or CD3≥1, CD138≤2 and iii) Fibroid- CD68 SL<2 and CD3, CD20, CD138<1.
Results: At baseline, the presence of synovial MCs was significantly associated with synovial inflammation (high synovitis score 60.7% in MC+ vs 16% in MC-, p<0.05) and lymphoid aggregates (lymphoid pathotype 64.4% in MC+ Vs 16.1% in MC-). Additionally, MCs were associated with systemic inflammation and disease activity (e.g. DAS-28 5.96 in MC+ vs 5.18 in MC-, p<0.05). Treatment with synthetic DMARDs induced a partial reduction in MC numbers (mean MC at baseline 14.2/mm2; at 6 months 8.2/mm2, p=0.094). Accordingly, synovial MCs were still present at 6 months in 45% of patients (9/20), in association with synovitis and lymphoid aggregates (high synovitis score and lymphoid pathotype 44.4% in MC+ vs 0% in MC-, p<0.05). Additionally, the presence of MCs at 6 months was associated with a higher DAS28 (4.08 in MC+ vs 2.41 in MC-, p<0.05) and a lower rate of remission (DAS28<2.6 22.2% in MC+ vs 72.7% in MC-, p<0.05).
Conclusion: Here we show that treatment with synthetic DMARDs in early RA patients partially reduces the number of synovial mast cells and their persistence (MC-rich synovitis) is associated with lack of response to DMARDs. This exploratory study confirms the relevance of MCs as part of the inflammatory infiltrate in the synovia of RA patients, warranting further investigations to clarify their role in disease progression and response to treatment.
To cite this abstract in AMA style:Rivellese F, Humby F, Pagani S, Nerviani A, Pitzalis C. Persistence of Mast Cell-Rich Synovitis Is Associated with Lack of Response to Synthetic Disease Modifying Anti-Rheumatic Drugs in Patients with Early Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/persistence-of-mast-cell-rich-synovitis-is-associated-with-lack-of-response-to-synthetic-disease-modifying-anti-rheumatic-drugs-in-patients-with-early-rheumatoid-arthritis/. Accessed May 29, 2020.
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