Abstract
The purpose of this study was to investigate the relationship between clinical disease activity in patients with advanced stage rheumatoid arthritis (RA) on treatment with Disease Modifying Antirheumatic Drugs (DMARDs) and histopathological scores of synovial inflammation. To this end, synovial biopsies of 62 RA patients who underwent surgery for either synovectomy or total joint arthroplasty were assessed by a general synovitis score (GSS) and an immunologic synovitis score (IMSYC). The clinical disease activity index (CDAI) was significantly correlated with both the GSS and the IMSYC (r = 0.65, p = <0.001, r = 0.68, p = <0.001). Compared to patients with moderate and high disease activity, there was a significantly lower expression of T cell (CD3), B cell (CD20) and neutrophil (CD15) markers in synovial tissue of patients with low activity, but similar expression of the macrophage marker CD68. Subgroup analyses revealed no differences between small and large joints, seropositive and seronegative RA and patients with or without prednisolone treatment. However, we found a significantly stronger correlation of CDAI with IMSYC in patients undergoing arthroplasty (r = 0.82) than in patients undergoing synovectomy (r = 0.55). In addition, there was a stronger correlation of CDAI with GSS in patients treated with methotrexate (r = 0.86) than in patients with TNFα blockade (r = 0.55). In summary, the present study demonstrates that the histopathological scores GSS and IMSYC in general reflect clinical disease activity in patients with advanced stage rheumatoid arthritis, but that there is some heterogeneity between subgroups of patients within the cohort. In the future, molecular characterization of synovial inflammatory cell populations, including plasma cell infiltrates, will help to further defined clinically important subtypes of RA and treatment response.
Highlights
Rheumatoid arthritis (RA) is the most prevalent autoimmune arthritis, affecting approximately 1% of the population
We demonstrate that in late-stage rheumatoid arthritis (RA) patients under MTX and TNF alpha blockade, both General Synovitis Score (GSS) and immunologic synovitis score (IMSYC) significantly correlate with the clinical disease activity
GSS has been established as an effective diagnostic tool to distinguish rheumatic and degenerative joint diseases, in particular osteoarthritis and rheumatoid arthritis
Summary
Rheumatoid arthritis (RA) is the most prevalent autoimmune arthritis, affecting approximately 1% of the population. Www.nature.com/scientificreports resulting in persistent synovitis[3] Most of these non- responders display persistent swelling of multiple joints and tendon sheaths[4]. The histopathological General Synovitis Score (GSS) has been developed in order to distinguish inflammatory arthritis from non-inflammatory arthritis[5]. This score considers three components of synovitis: lining layer hyperplasia, activation of resident cells (stroma) and inflammatory infiltrate. The purpose of this study was to assess the correlation of the synovitis scores GSS and IMSYC with the clinical disease activity of 62 DMARD treated late stage RA patients
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