PO:06:094 | Exploring the relationship between inflammation and collagen deposition in synovial tissue and clinical outcomes in active arthritis: insights from a monocentric pilot study

Dario Bruno¹, Barbara Tolusso¹, Daniela Renna¹, Mohamed Hegazi², Fabio Pasqualini², Marta Caprioli¹, Giacomo Maria Guidelli¹, Tommaso Hubert³, Nicoletta Luciano^1|3, Marzia Monferini³, Natasa Isailovic³, Fabio Grizzi^2|3, Salvatorelorenzo Renne³, Costantino Pitzalis^1|3|4, Elisa Gremese^1|3. | ¹Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano (MI); ²Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Milano; ³Department of Biomedical Sciences, Humanitas University, Rozzano (MI), Italy; ⁴Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, UK

Background. Synovial collagen remodelling may mirror chronic inflammation and repair processes, potentially serving as a structural correlate of disease activity in arthritis. Based on this, the aim of this study was to investigate the relationship between synovial inflammatory histopathology and collagen remodelling in patients with active rheumatoid arthritis (RA) or psoriatic arthritis (PsA).

Methods. US-guided synovial biopsies were obtained from inflamed joints (knee/wrist) in 30 patients (18 RA, 12 PsA) with active arthritis, undergoing therapeutic re-evaluation.Synovial inflammation was evaluated considering Krenn Synovitis Score (KSS), immunohistochemical analysis (sublining CD68, CD3, CD20, CD138), pathotype classification, and evaluation of neutrophil infiltration.For 12 patients (RA, PsA),3-micrometer sections were stained with fresh Picrosirius red,then digitized via brightfield and polarized light microscopy for morphometry and collagen typing.Stained area and collagen maturation index were quantified using computer-aided image analysis.Clinical disease activity was recorded at baseline and at 3-month follow-up.

Results. The mean age of patients was 52 years and 64.5% were female;the mean disease duration was 5.6 years. Mean KSS was 4.5±0.5 in RA and 4.2±0.5 in PsA. 17 (56.7%) patients were classified as lympho-myeloid, 10(33.3%) as diffuse-myeloid,and 3(10%) as pauci-immune pathotype.Moreover, neutrophil infiltration of ST was present in 12(40%) of the overall cohort and was associated with higher KSS (p = 0.003).Higher KSS also tended to correlate with the number of previous bDMARDs, and pathotype distribution differed by prior biologic exposure (p = 0.029);notably, patients with a pauci-immune synovitis had received the highest number of previous bDMARDs. Considering collagen deposition,the mean collagen area was 39.48±7.52% in RA and 40.79±12.09% in PsA, while the mean collagen maturity index was 0.73±0.04 and 0.72±0.03, respectively.No associations were found between collagen parameters and sex, age, disease duration, or biopsy site. In RA, collagen area showed a trend toward inverse correlation with CD68+ macrophage infiltration (p = 0.057). In PsA, both collagen area and maturation index were inversely correlated with inflammatory infiltrate, B cells, and plasma cells (all p = 0.04). Additionally, disease duration in PsA was positively associated with both collagen area(p = 0.025) and collagen maturity index (p = 0.017), suggesting that long-standing disease may promote extracellular matrix stabilization. Importantly, a significant inverse correlation between collagen area and collagen maturity index was observed in RA (p = 0.047). At 3-month follow-up, histological pathotype was associated with DAS28 response: responders more frequently showed a diffuse-myeloid profile, while no responders were mostly observed among pauci-immune cases.

Conclusions. Synovial immune cell infiltration is associated with collagen remodelling in both RA and PsA, with distinct patterns linked to disease duration and tissue organization.The inverse correlation between collagen area and maturity in RA suggests matrix expansion during active synovitis.