Patient Outcomes in OA Linked to Synovial Fluid Monocyte, Macrophage Subsets

Researchers sought to determine whether levels of synovial fluid monocyte/macrophage subsets affect joint function and quality of life in patients with osteoarthritis.

Heterogeneous mixtures of monocytes and macrophages (monocytes/macrophages) in synovial fluid were linked to knee osteoarthritis (OA) stiffness, joint function, and quality of life (QoL) and exhibited an activated phenotype,  according to results of a cohort study published in Arthritis Research & Therapy.

Because monocyte/macrophages are known to be abundant in OA joints and to be involved in the progression of OA, the investigators sought to explore whether synovial fluid monocyte/macrophage subsets are indicative of QoL and joint function in patients with OA, which could serve as biomarkers and therapeutic targets for the disease. Different subsets of OA monocytes/macrophages have not been analyzed in detail, particularly with respect to their relationship with patient-reported outcome measures (PROMs).

This study characterized synovial fluid leukocytes (n=86) and peripheral blood mononuclear cells (n=53) from patients with OA. Immunoassays were used to detect soluble monocyte/macrophage receptors and chemokine (sCD14, sCD163, CCL2, CX3CL1) levels in synovial fluid. The researchers used linear models adjusted for age, sex, and body mass index to establish the associations between synovial fluid monocyte/macrophage subsets and soluble factors with PROMs (n=83).

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Study results showed that synovial fluid monocytes/macrophages were the most abundant synovial fluid leukocytes detected. Within these synovial fluid leukocytes, the double-positive CD14+CD16+ monocyte/macrophage subset is enriched in knee OA compared with the circulation. In fact, monocyte/macrophage subset ratios were associated with PROMs, particularly stiffness, function, and QoL. Of note, the SF CD14+CD16+  monocyte/macrophage subset ratio correlated with synovial fluid chemokine (C-C motif) ligand 2 (CCL2) levels but not with sCD163 or sCD14 levels. Moreover, no association was demonstrated between PROMs and synovial fluid CCL2, sCD163, sCD14, or CX3CL1, which was below detection levels.

All synovial fluid monocytes/macrophages exhibited high levels of human leukocyte antigen-antigen D-related (HLA-DR), which is indicative of an activated phenotype. A correlation between OA synovial fluid monocyte/macrophage subsets and activated CD4+ T-cell subsets implies modulation of CD4+ T-cell activation by monocyte/macrophages.

The researchers concluded that SF monocyte/macrophage subsets are linked to knee OA PROMs and demonstrate an activated phenotype, possibly leading to modulation of CD4+ T-cell activation. The association of synovial fluid monocyte/macrophage subsets with knee OA stiffness, joint function, and QoL endorses a biologic role for monocyte/macrophage subsets in knee OA inflammation, which warrants additional investigation.


Gómez-Aristizábal A, Gandhi R, Mahomed NN, Marshall KW, Viswanathan S. Synovial fluid monocyte/macrophage subsets and their correlation to patient-reported outcomes in osteoarthritic patients: a cohort study. Arthritis Res Ther. 2019;21(1):26.