POS0139 RELATIONSHIP BETWEEN SYNOVIAL FLUID IMMUNE CELL PHENOTYPES AND CLINICAL OUTCOMES IN PATIENTS WITH KNEE OSTEOARTHRITIS

Abstract

BackgroundKnee osteoarthritis (KOA) is a highly heterogeneous and multifaceted disease with many clinical phenotypes that often overlap. So far, phenotypes based on the composition of immune cells in synovial fluid (SF) have not yet been defined, although these cells, their activation and the mediators they produce play a central role in the pathophysiology of OA.ObjectivesThis study aimed to investigate the relation between SF-derived immune cells and SF protein patterns in patients with KOA and its relationship to disease trajectory. Special emphasis was given to chemokine receptor expression on macrophages.MethodsImmune cell phenotype and protein pattern from 119 KOA patients were analysed using flow cytometry. KOA phenotypes were determined by multivariate network analysis and related to clinical outcome 3-6 months post-sampling. The chemokine receptor pattern on macrophages was analysed using the FlowSOM algorithm and verified by manual gating.ResultsFour KOA-phenotypes were detected based on the distribution of T-lymphocytes, monocyte-macrophage lineage cells and activated CD8+ T-lymphocytes. The “healing” phenotype (n=17) had a high proportion of T lymphocytes, but low NK cells, monocyte-macrophage lineage and neutrophils, showing improved symptoms in 70% of patients. The “pain-less” phenotype (n=31) characterised by a higher percentage of neutrophils and a lower percentage of lymphocytes and monocyte-macrophage lineage as well as its activation, showed lower levels of pain. Next, the “progressive” phenotype (n=35) was represented by high NK percentage and monocyte-macrophage lineage representation yet low lymphocyte percentage and T-lymphocyte activation. From the „inflammatory progressive” phenotype (n=36) with a high proportion of activated lymphocytes, macrophages, NK cells and neutrophils, only 39% of patients improved during follow-up. The phenotypes obtained showed differences in CXCL10 expression, with high levels in the “healing” KOA1 compared to the “inflammatory progressive” KOA4 phenotype (1106 vs 126 pg/ml, p=0.001). In general, high CXCL10 levels were associated with improved disease trajectory compared to patients with worsening symptoms (339 vs 222 pg/ml, p=0.002). CXCL10 levels in patients with improved symptoms showed a decreasing trend between phenotypes from KOA1 > KOA2 > KOA3 > KOA4. Regarding macrophages, low expression of chemokine receptors CXCR4 and CCR7 on macrophages was associated with improved symptoms regardless of KOA phenotype.ConclusionWe identified four KOA phenotypes differing in immune cell percentage and activation associated with different clinical trajectories. Low expression of chemokine receptors CXCR4 and CCR7 on macrophages and high CXCL10 in SF was linked to KOA symptom improvement. How these phenotypes can be targeted therapeutically deserves future investigations.AcknowledgementsNU20-06-00269, NU21-06-00370, MH_CZ-DRO (FNOL,_00098892), IGA_LF_2022_011Disclosure of InterestsNone declared