Background/Purpose: Patients with meniscal injury are at increased risk for symptomatic knee osteoarthritis (OA), and often already have intraoperative signs of early-stage cartilage degradation. We previously reported that patients with meniscal tears often exhibit synovial inflammation, which is associated with more severe knee symptoms. We further demonstrated that synovitis was associated with expression of mRNA for CCL19, a lymphocyte chemoattractant, and its receptor CCR7. Others have reported a relationship between MCP-1, a macrophage chemoattractant, and knee pain in patients with knee injuries including meniscal tears. We sought to determine whether CCL19 and MCP-1 are measurable in synovial fluid (SF) of patients undergoing meniscal arthroscopies, and if protein levels are associated with knee symptoms or dysfunction. We also investigated expression patterns of CCR7 (CCL19 receptor) and CCR2 (MCP-1 receptor) within synovium to gain insight into the cell types that might be responsive to these factors.

Methods: We recruited subjects undergoing arthroscopy for meniscal tears. SF CCL19 and MCP-1 were measured by ELISA (R&D systems). Knee symptoms and dysfunction were preoperatively assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS), consisting of 5 subscales measuring pain, other knee symptoms, function in daily living (ADL), recreational activities, and quality of life. Associations with KOOS scores were tested using Pearson correlations. Multivariate linear regression models adjusted for age, gender, BMI, and degree of radiographic OA (Kellgren-Lawrence scores). Synovial CCR7 and CCR2 expression was characterized using immunohistochemical (IHC) staining, and compared to staining patterns in synovium from asymptomatic organ donors.

Results: 32 patients with meniscal tears were included. Median age (IQR) was 55 (47-61), and gender ratio M:F was 17:15. CCL19 was detectable in 25/32 (78%) while MCP-1 was detectable in all patients. Mean concentration+/-SD of CCL19 was 374.28+/-367.58 pg/mL, and MCP-1 was 450.13+/-273.85 pg/mL. CCL19 concentration correlated with worse KOOS-ADL subscores (Pearson r= -0.362, p=0.049), but was not independent of other factors in adjusted regression analyses. In the model, BMI was an independent predictor of KOOS-ADL subscores (p=0.01), and there was a correlation between BMI and CCL19 levels (Pearson r=0.430, p=0.02).  MCP-1 levels did not correlate with KOOS subscores. IHC staining identified CCR7 expression in the synovial lining layer, endothelium, and perivascular inflammatory infiltrates, while CCR2 expression was identified primarily in the lining layer. CCR7 and CCR2 staining was more pronounced in patients with meniscal tears than in asymptomatic organ donors.

Conclusion: In patients with meniscal tears, CCL19 and MCP-1 are detectable in SF. Although SF CCL19 was not an independent predictor of knee symptoms, CCL19 may be related to increased BMI. CCR7 did appear increased in meniscal tear patients, and its expression by multiple cell types in synovium suggests that CCL19/CCR7 activity may be involved in development of synovial changes seen in these patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/synovial-expression-of-ccl19-mcp-1-and-their-receptors-in-patients-with-meniscal-injury-variability-and-relationship-with-knee-symptoms/