Monocyte/macrophages in osteoarthritic synovial fluid are correlated with patient-reported outcomes

Gomez-Aristizabal, Alejandro 1, 2, 3; Gandhi, Rajiv 2; Marshall, Kenneth 2; Mahomed, Nizar 2; Viswanathan, Sowmya 1, 2, 3, 4

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 
2. Arthritis Program, Krembil Research Institute, Toronto Western Hospital; 
3. Cell Therapy Program University Health Network; 
4. Division of Hematology, Department of Medicine, University of Toronto

Osteoarthritis (OA) is a progressive and debilitating joint disease with high prevalence. OA involves chronic, low-grade inflammation of the synovium (synovitis). Inflammatory cells, particularly monocytes/macrophages (MΦs) are abundantly present in OA synovium and involved in OA progression. However, the types of MΦs present in the OA synovial fluid (SF) have not been investigated and the relationship between SF cells and patient symptoms have not been previously deciphered. We hypothesize that levels of SF-resident MΦ subsets are indicative of symptomatic OA.
Methods: Synovial fluid leukocytes (SFLs, N=81) and peripheral blood mononuclear cells (PBMCs, n=51) from OA patients were characterized. Linear models were used to determine the correlation between SF MΦs with patient-reported and radiographic outcomes; these models were adjusted for sex, age and body mass index. 
Results: SF MΦs (36.5%) are the most abundant SFLs and are present in an activated state. Within these, inflammatory MΦs (CD14+CD16+, 39.2% vs 5.9% in circulating MΦs) are more abundant in the SF than circulation. Levels of CD14+CD16+ MΦs, which express high levels of PAR2 (61.5% PAR2+), a receptor involved in OA pain, correlates with worse patient-reported function, pain during locomotion and stiffness (β>0.38), but not with radiographic outcomes. 
Conclusion: Prevalence of SF MΦ correlates with clinical outcomes, respectively and is indicative of symptomatic OA phenotype, and may serve as means to objectively measure OA therapy outcomes and targets of novel therapeutics.