Synovial macrophages drive severe joint destruction in established rheumatoid arthritis

To investigate the synovial pathological predictors associated with the progression to severe bone erosion in patients with established rheumatoid arthritis (RA). This retrospective study analyzed 41 active RA patients with a disease duration of more than 24 months at our center between March and December 2023. All of these patients underwent synovial biopsy to obtain synovial tissue. These patients were divided into two groups (mild group and severe group) based on the severity of bone erosion assessed by plain X-ray. HE and immunohistochemical staining for CD3, CD20, CD68, and CD138 were conducted on synovium. Stained cells positive for these markers were observed under microscope. the number of positive cells per 20× high-power field in the sublining layer was recorded for each marker. The mild group consisted of 25 patients (23 females) with a median age of 58 years and a median disease duration of 114 months. The severe group included 16 patients (13 females) with a median age of 56 years and a median disease duration of 120 months. There were no significant differences between the mild and severe groups in terms of age, gender, disease duration, RF, ACPA, ESR, and CRP (P > 0.05). However, the disease activity score in 28 joints (DAS-28) of severe group were significantly higher than mild group (5.16 vs. 4.53, P = 0.010). Inflammatory infiltration score observed with HE staining was significantly higher in severe group (P = 0.033), whereas synovial hyperplasia, neovascularization, and stromal activation did not show significant differences between the two groups. The results of immunohistochemistry revealed significantly higher expression of synovial CD68-positive cells in severe group. Multivariable logistic regression analysis showed that synovial CD68-positive cells (OR = 1.020, P = 0.011) were independent risk factors for progressive bone erosion in RA. Synovial macrophage infiltration is an independent risk factor leading to severe progression of bone erosion in RA.