Synovial fluid monocyte/macrophage subsets and their correlation to patient-reported outcomes in osteoarthritic patients: a cohort study

BackgroundChronic, low-grade inflammation of the synovium (synovitis) is a hallmark of osteoarthritis (OA), thus understanding of OA immunobiology, mediated by immune effectors, is of importance. Specifically, monocytes/macrophages (Ms) are known to be abundantly present in OA joints and involved in OA progression. However, different subsets of OA Ms have not been investigated in detail, especially in terms of their relationship with patient-reported outcome measures (PROMs). We hypothesized that levels of synovial fluid (SF) M subsets are indicative of joint function and quality of life in patients with OA, and can therefore serve as biomarkers and therapeutic targets for OA.Methods p id=Par2 In this cohort study, synovial fluid leukocytes (SFLs, N=86) and peripheral blood mononuclear cells (n=53) from patients with knee OA were characterized. Soluble M phi receptors and chemokine (sCD14, sCD163, CCL2, CX3CL1) levels were detected in SF using immunoassays. Linear models, adjusted for sex, age and body mass index, were used to determine associations between SF M phi s and soluble factors with PROMs (N=83). Pearson correlation was calculated to determine correlation between M phi subsets, T cells and soluble factors.Results p id=Par3 SF M phi s were the most abundant SFLs. Within these, the double-positive CD14(+)CD16(+)-M phi subset is enriched in knee OA SF compared to the circulation. Importantly, M phi subset ratios correlated with PROMs, specially stiffness, function and quality of life. Interestingly, the SF CD14(+)CD16(+)-M phi subset ratio correlated with SF chemokine (C-C motif) ligand 2 (CCL2) levels but not with levels of sCD163 or sCD14; we found no association between PROMs and either SF CCL2, sCD163, sCD14 or CX3CL1 (which was below detection levels). All SF M phi s displayed high levels of HLA-DR, suggesting an activated phenotype. Correlation between OA SF M phi subsets and activated CD4(+) T cell subsets suggests modulation of CD4(+) T cell activation by M phi s.Conclusion p id=Par4 SF M phi subsets are associated with knee OA PROMs and display an activated phenotype, which may lead to modulation of CD4(+) T cell activation. Knee OA SF M phi subsets could serve as knee OA function biomarkers and as targets of novel therapeutics.