gms | German Medical Science

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Characteristic of the disease is an inflamed synovium and destruction of cartilage and bone. Since there is no cure for the disease, the therapeutic goal is remission. However, knowledge of remission and its underlying characteristics is limited and needs to be better characterized.

Objectives: Characterization of remission in RA by comparison of histological and molecular features in the synovium of active RA patients compared to remission.

Methods: RA patients (43–81 years) were classified as active or in remission after joint replacement surgery based on laboratory (e.g. ESR, CRP, leucocytes) or clinical parameters (e.g. painful joints, pain, medication). The Krenn score was used to assess synovitis. To study remission at RNA level, RASF from both patient groups were stimulated with IL-1 for 24 hours and analysed by RNA sequencing. Evaluation included analysis of differentially expressed genes (DEG) based on a combination of absolute expression, divergence and significance as well as gene set enrichment analysis of DEGs.

Results: Clinical classification of the RA patients resulted in the inclusion of 20 active and 19 patients in remission. Patients in remission showed lower values in the Krenn score regarding hyperplasia (P=0.021) and total Krenn score (P=0.022). Sub-analyses regarding the medication (e.g. biologicals, DMARDs, NSAIDs, glucocorticoids) showed a significant reduction of hyperplasia with biologics (4.2-fold decrease). RNA sequencing indicated homogeneity of expressed genes and the underlying pathways between remission and active RA patients. These results were evident in both the unstimulated approach and the stimulated RASF. However, RNAseq identified several DEGs including IL-36B (-0.12-fold), cathepsin K (-0.60-fold) and folliculin (-0.65-fold) which were downregulated in remission and play a crucial role in RA progression.

Conclusion: To investigate the histologic and molecular differences that might better characterize remission in RA, the synovium of patients after joint replacement surgery was examined. Histological examination showed lower values for inflammation and hyperplasia, especially in patients receiving biologics. RNA sequencing showed altered gene expression of proinflammatory genes with lower expression in patients in remission. Especially genes of the proinflammatory IL-36 family seem to play an important role in achieving remission.