Cytokine Expression In Trapeziometacarpal Osteoarthritis: Predicting Prognosis, Progression And Treatment
Heather L. Baltzer, MD, MSc, FRCSC, FACS, Anusha Ratneswaran, PhD, Daniel Antflek, BSc, Jason Rockel, PhD, Konstantin Shestopaloff, PhD, Mohit Kapoor, MSc, PdD.
University of Toronto, Toronto, ON, Canada.
PURPOSE: A tremendous interest exists in defining the role of inflammatory cytokines in patients with symptomatic osteoarthritis (OA) for prognostic, personalized therapeutic and regenerative purposes. Our overall objective is to discover which cytokines are capable of differential disease stratification through the longitudinal characterization of trapeziometacarpal (TM) OA patients.
METHODS: This prospective, longitudinal cohort of TM OA patients collects clinical outcomes (patient-reported pain and function), demographics, and plasma at multiple timepoints. Baseline plasma inflammatory cytokine panel screening was performed using Multiplex analysis. Principal component analysis (PCA) was used to identify cytokine clustering patterns. Baseline inflammatory cytokines were compared between surgical and non-surgical cohorts of patients. In surgical patients, inflammatory cytokine levels were compared from baseline to 3 months post-surgery and correlated to patient-reported pain (McGill Pain Questionnaire). Comparative analyses used independent sample t tests and χ2 tests as appropriate. The Pearson correlation coefficient was calculated for correlative relationships.
RESULTS: The cohort (N = 73) was primarily female (74%), mean age of 58.9 (±17) with median Eaton-Littler Radiographic score = 3. An unbiased subset of clustered cytokines in plasma may represent an inflammatory phenotype among a TM OA subpopulation (elevated G-CSF, Il-1B, TNFa, Il-10, Il- 17A, Il12p70, MCP-1, Il-6 and VEGF). Within this cohort, surgical patients had significantly elevated levels of inflammatory cytokines (GM-CSF, IL-7, IFNγ, IL1-RA and MCP-1) compared with non-surgical patients (p < 0.05). Among the surgical patients, numerous inflammatory and anti-inflammatory cytokines were changed after intervention and showed significant correlation to improved pain scores (e.g. IP-10, r2=0.23; VEGF, r2=0.25; p<0.05). At one year following surgery, two circulating cytokines (GM-CSF and IL-7) changed to levels comparable to the non-surgical cohort at baseline (p>0.05).
CONCLUSION: These preliminary data suggest that there may exist TM OA phenotypes based on cytokine profiles. Observed cytokine responses demonstrate different potential phenotypes that may be useful for predicting response to treatment. Definitive associations of cytokine expression profiles to disease phenotype and treatment response will require a greater number of patients as this longitudinal TM OA cohort and biobank continues to grow.
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