Background/Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which leads to local and systemic manifestations. Subsequently, the inflamed synovium drives the destruction of cartilage and bone in the affected joints. Until now, remission has been considered the therapeutic goal of the disease, as RA cannot be cured. However, as the prognostic outcomes of patients vary significantly, a better understanding of remission is required.

Objectives: To characterize remission in RA comparing histological and molecular features of active RA patients to those in remission in the synovium.

Methods: RA patients (35-82 years) were classified as active or remission after joint replacement surgery based on clinical (e.g. painful joints, pain degree, medication) and laboratory (e.g. ESR, CRP, leucocytes) parameters. To characterize synovitis, the Krenn score was used, and immunofluorescence with CD90 and podoplanin antibodies was performed. On RNA level, RNA sequencing of RA synovial fibroblasts (RASF) was performed, which were previously stimulated with IL-1ß for 24 hours. Differentially expressed genes (DEGs) were analysed based on a combination of absolute expression, divergence and significance. To identify enriched gene sets and pathways, a gene set enrichment analysis of DEGs was performed.

Results: 64 RA patients (29 active, 35 in remission) were included in the Krenn score analysis. Reduced values especially for hyperplasia (p=0.001) as well as for infiltrates (p=0.0001) and the general degree of inflammation (p < 0.0001) was observed in the remission group. Subanalyses of medication (e.g. biologicals, DMARDs, NSAIDs, glucocorticoids) confirmed differences between remission and active RA for all drugs and indicated an overall reduction of hyperplasia observed most strongly in the biologics group (p=0.0008). The fibroblast markers podoplanin (marker for fibroblasts located mainly in the lining) and CD90 (marker for fibroblasts located mainly in the sublining) showed the greatest differences indicating patients in remission have fewer numbers of fibroblasts in both, the lining and the sublining layer. Patients in remission showed several differentially expressed genes that were lower in remission compared to active RA patients, including e.g. IL-36ß and its corresponding receptor antagonist. As those cytokines play a role in chronic inflammatory processes and the progression of RA, the impact of these factors on RASF of patients in remission compared to active RA are of especial interest.

Conclusion: The characterization of synovium after joint replacement surgery was used to compare histological and molecular differences that may help to characterize remission in RA. The histology showed a lower degree of inflammation and, most prominent, hyperplasia for patients in remission, specifically in patients receiving biologics. RNAseq identified several genes showing altered expression pattern related to the pro-inflammatory and destructive processes during RA which gives insight into the molecular characteristics.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/histological-and-molecular-comparison-in-the-synovial-tissue-of-patients-with-active-rheumatoid-arthritis-to-remission/