Background/Purpose:

In patients with knee osteoarthritis (OA), synovitis is associated with severity of knee symptoms. Previously, we demonstrated that in patients undergoing partial meniscectomy without radiographic OA, synovitis is associated with worse preoperative knee pain and function using the Lysholm score, which measures knee-specific pain and disability on a single scale. mRNA expression levels of the chemokine CCL19 and its receptor CCR7 were associated with presence of synovitis, and strongly correlated with worse Lysholm scores. However, unlike the patients in our previous study, most patients with meniscal tears indicated for arthroscopy already have pre-existing cartilage degeneration indicative of early-stage OA. In this study we sought to validate these markers in more typical patients presenting for arthroscopy to determine their utility as markers of more symptomatic early knee disease. To measure knee specific pain and functional deficits we used the Knee Injury and Osteoarthritis Outcome score (KOOS).

Methods:

Synovial biopsies were collected during surgery from 19 patients undergoing arthroscopic meniscal procedures. Relative mRNA expression levels (RE) of CCL19 and CCR7 were measured using Real Time polymerase chain reaction. The KOOS was administered preoperatively and measures knee function and disability on 5 separate domains: Pain, symptoms, activities of daily living (ADL), sport and recreation function, knee-related quality of life (QOL). Pearsons correlations were used to determine relationships between mRNA levels and KOOS scores.  Multivariable linear regression models were run to test if associations were independent of age, gender, BMI, cartilage degeneration (measured using Outerbridge Classification) and radiographic OA (Kellgren-Lawrence (K/L)) scores. Post-hoc power analysis showed our study was powered at 73% to detect a moderate correlation (ρ = 0.5) between chemokine levels and KOOS scores.

Results:

The majority of patients had grade 2-4 Outerbridge scores and median K/L scores of 2, indicative of pre-existing OA.  CCL19 and CCR7 transcripts were detected in all patients.  Unadjusted analysis revealed CCL19 RE was associated with KOOS ADL (r = -0.620, p = 0.005), Pain (r=-0.547, p=0.015), and QOL scores (r=-0.479, 0.038). Adjusted analyses showed CCL19 RE was independently associated with KOOS ADL scores (β = -4.201, 95% CI [-8.071, -0.331], p = 0.036). Trends were observed for associations with KOOS Pain (CCL19 β = -3.252, 95% CI [-6.748, 0.243], p = 0.065) and KOOS QOL CCL19 β = -3.719, 95% CI [-7.786, 0.349], p = 0.070).

Conclusion:

CCL19 is important in lymphocyte recruitment and was identified in our previous work as a marker of synovitis. Our current work extends these findings by demonstrating a relationship between CCL19 expression and knee-related difficulty with activities of daily living in typical patients presenting for arthroscopic meniscal surgeries. These findings increase the potential for this marker to be useful in identifying patients with synovitis after a meniscal tear and with early-stage OA. Future work is needed to determine the role of this marker in development and pathogenesis of symptomatic OA after meniscal injury.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/synovial-inflammation-in-meniscal-tear-patients-ccl19-mrna-expression-is-independently-associated-with-knee-related-disability/