Background The presence of ectopic lymphoid-like structures (ELS) within the synovial tissue of a cohort of patients with inflammatory arthritis is well recognised. There is also data supporting the concept that these structures are immunologically competent and can support chronic inflammation within the joint. There is limited data however examining whether the presence of ELS associates with specific clinical phenotypes in early arthritis.
Objectives The aim of this study was therefore to investigate whether synovial ELS associated with specific clinical phenotypes in an early arthritis cohort.
Methods A cohort of DMARD-naïve early arthritis (<12 months duration, at least 1 swollen joint) patients recruited at Barts and The London Hospital, as part of the MRC-funded Pathobiology of Early Arthritis Cohort (PEAC) http://www.peac-mrc.mds.qmul.ac.uk/ were included in the analysis. The study was approved by the ethics committee (REC). Baseline disease characteristics assessed included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, rheumatoid factor (RF), anti-cyclic-citrullinated peptide antibodies (anti-CCP) and 28 joint-disease activity score (DAS28). All patients underwent ultrasound-guided synovial biopsy of an affected joint at baseline. Sections of paraffin embedded RA synovial tissue were stained with standard Haematoxylin and Eosin (H&E) and graded as either a diffuse or aggregate synovitis. In addition sequentially cut paraffin sections underwent immunohistochemical staining for B-cells(CD20), T cells (CD3) and macrophages(CD68) and were semi-quantitatively scored (0-4) for each marker.
Results 84 sequentially recruited patients with both synovial tissue and a complete clinical data set were included within the analysis (61% female, mean age 50). 64% (n=57) of patients were classified as diffuse and 36% (n=27) as aggregate. The presence of synovial lymphocytic aggregates was significantly associated with higher synovial infiltration of T cells, B cells, plasma cells and both lining and sublining macrophages (p<0.001). Moreover, the presence of synovial aggregates was significantly associated with baseline RA diagnosis (1987 ACR criteria), positive ESR/CRP and seropositivity for RF and anti-CCP antibodies. Interestingly, there was also a significant correlation between a higher synovial infiltration of B cells and plasma cells and positivity for anti-CCP antibodies (p=0.002 and p<0.001) and RF (p<0.001 and p<0.001) in the serum.
Conclusions The significant association of synovial ELS with the diagnosis of RA and sero-positivity for RF and anti-CCP antibodies in early arthritis stronlgly supports the concept that these structures are functional and involved in disease pathogenesis. In addition these observations also suggest that baseline synovial pathotype may have a role as a prognostic biomarker in early arthritis.
Disclosure of Interest None Declared