Background/Purpose: Osteoarthritis (OA) is a progressive joint disease driven by a blend of inflammatory and biomechanical processes. Studies using human samples to understand inflammatory mechanisms in OA frequently recruit OA patients with different affected joints, even though recent evidence indicates that OA is a heterogeneous disease which only culminates in a common end point. Differences in age of onset and the dynamics of disease progression suggest that different joints may represent different disease entities, thereby diluting the discovery potential in a combined analysis. We hypothesized that different OA joints may also differ in immunopathology within the synovium.

Methods: We profiled the immune cell composition (flow cytometry) and cytokine release profiles (ELISA) in purified mononuclear cells from the synovial membrane from 51 patients undergoing either hip (n = 34) or knee (n = 17) replacement surgery. Peripheral blood was collected simultaneously and profiled using flow cytometry. Overall, 48 different cytokines were assayed. Unsupervised computational approaches were used for disease deconstruction.

Results: Hip and knee osteoarthritis were not identical with respect to the inflammatory processes that take place in the synovial membrane. The mononuclear cell infiltration pattern in the synovial membrane was highly variable between individuals, ranging from a CD4+ T cell predominant phenotype to a macrophage predominant phenotype. When directly comparing hip and knee samples, we found that macrophages and CD8+ T cells were expanded fourfold in the synovial membrane of patients with knee OA compared to hip OA, while CD4+ T cells, B cells and NK cells were found at comparable quantities. In contrast, there were no differences in immune cell abundance in the peripheral blood.
Consistent with differences in mononuclear cell infiltration into the joints, we identified differences in the cytokine release profile of cultured cells. Upon isolation and culture of cells from synovial membrane over 24 hours, isolates from hip OA released higher concentrations of Eotaxin (CCL11), G-CSF, GM-CSF, IFN-γ, IP-10 (CXCL10), TNF-α, MIP-1α (CCL3), MIP-1β (CCL4), IL-4, IL-10, IL-17 and lower concentrations of stem cell factor (SCF), thereby highlighting the difference in nature of hip and knee osteoarthritis.

Conclusion: Osteoarthritis affecting different joints has often been regarded as the same disease. This study provides evidence that hip and knee OA are immunologically distinct types of OA, warranting further investigation of different subtypes of OA. Further, this public resource of the cytokine expression landscape and mononuclear cell infiltration pattern of patients with hip and knee osteoarthritis will help accelerate research on the immunobiology of osteoarthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/divergent-mononuclear-cell-participation-and-cytokine-release-profiles-define-hip-and-knee-osteoarthritis/