Pos1353 semiquantitative assessment of knee osteoarthritis-related synovitis compared to chronic inflammatory arthritides: relation to age and impact on bone/structural damage

Background Knee Osteoarthritis (KOA) is one of the most frequent causes of pain and disability, representing a relevant clinical burden. Although it was largely considered a mostly mechanical-based pathology, low-grade synovial inflammation was found to contribute to radiographic progression and pain chronicity [1] . Objectives To evaluate the histological characteristics of synovial membrane inflammation in KOA patients compared to chronic inflammatory diseases as Rheumatoid (RA) and Psoriatic Arthritis (PsA) across disease phases. Methods 170 patients with KOA, 240 patients with RA, 92 patients with PsA naive to pharmacological treatments and 200 patients with RA in sustained clinical and ultrasound remission (RA-r) underwent ultrasound-guided synovial biopsy of the knee and conventional X-rays. None of enrolled KOA patient had evidence of inflammatory condition (including chronic inflammatory diseases and crystal related arthritis). Synovial membrane samples were processed for histology (hematoxylin-eosin staining) for the semiquantitative assessment of synovitis degree (Krenn synovitis score [2] - KSS). Moreover, this analysis was implemented with the semiqualitative assessment of presence/absence of synovial lymphocytes, plasmacells, myxoid degeneration and inflammatory perivascular aggregates. X-rays were scored for Kellgren-Lawrence score [3] (KLs) assessment. Results RA and PsA patients naive to pharmacological treatment showed higher degree of synovial inflammation than patients with KOA as well as more likely presence of lymphocytes and plasmacells aggregates. Considering the whole KOA population, total KSS directly correlated with age (R²=0.041; p=0.008), thickness of synovial membrane (R²=0.115; p<0.001) and Power Doppler score (R²=0.142; p<0.001) at ultrasound evaluation, VAS pain (R²=0.025; p=0.039) and KLs (R²=0.54; p<0.0001). Stratifying KOA patients based on age categories, KOA patients aged ≥70 years had higher KSS (mean ±SEM, 2.46 ±0.179) and KLs (2.14 ±0.17) than younger KOA patients (KSS 1.98 ±0.113, p=0.0182 and KLs 1.25 ±0.101, p<0.001). To distinguish residual inflammation from osteoarthritis-related synovitis, we compared KOA-derived synovial tissues with the ones of RA-r patients, showing that the degree of KOA-related synovitis is significantly higher (mean ±SEM, 2.10 ±0.09) than the subclinical residual synovitis detected in RA-r patients (1.77 ±0.08, p=0.0103). Conclusion KOA-related synovitis represents an unmet clinical need due to still uncovered pathogenetic mechanisms. The severity of KOA-related synovitis impacts on bone structural damage and is related to age, supporting the role of inflammageing in KOA pathogenesis. References [1]Sanchez-Lopez, E., Coras, R., Torres, A., Lane, N. E. & Guma, M. Synovial inflammation in osteoarthritis progression. Nature Reviews Rheumatology vol. 18 Preprint at https://doi.org/10.1038/s41584-022-00749-9 (2022). [2]Krenn, V. et al. Synovitis score: Discrimination between chronic low-grade and high-grade synovitis. Histopathology 49 , (2006). [3]KELLGREN, J. H. & LAWRENCE, J. S. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16 , (1957). Acknowledgements: NIL. Disclosure of Interests None Declared.