Immune Cell Composition and Protein Biomarkers Correlate With PRP Treatment Outcomes in Knee Osteoarthritis

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Background: Current treatments for osteoarthritis (OA) include physical therapy, nonsteroidal anti-inflammatory drugs, and joint arthroplasty, which aim to address symptoms rather than modify disease progression. Autologous platelet-rich plasma (PRP) and other biologics administered in the affected joint are widely used as alternatives that are believed to alleviate symptoms. However, PRP's effectiveness in reducing knee OA pain is inconsistent across the literature, and the specific therapeutic components remain unclear. Purpose: To identify whether specific cellular and protein biomarkers correlate with patient-reported outcomes and can therefore serve as predictive biomarkers for PRP effectiveness. Study Design: Case series; Level of evidence, 4. Methods: PRP samples from 30 patients (30 knees) with knee OA (Kellgren & Lawrence grades 2-3) who were undergoing PRP treatment were analyzed to identify biomarkers associated with response. Blood samples were drawn, and 2 identical PRP samples were prepared, with one set used for therapy and the other for analysis. Component analysis included cell counts, immune cell, and platelet characterization via mass cytometry, along with proteomic analysis using mass spectrometry. Clinical outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS) and Patient-Reported Outcomes Measurement Information System patient reported outcomes at baseline and up to 6 months postinjection. Results: PRP therapy improved pain in 19 of 30 patients at 6 weeks postinjection (mean ± SD age, 56.04 ± 10.56 years): Several distinct immune cell clusters (T helper 1 CD4 T cells ( r = 0.44; P < .05), Central memory CD4 T cells ( r = 0.46; P < .05), Effector memory CD4 T cells ( r = 0.52; P < .05), and CD8 T cells ( r = 0.44; P < .05) positively correlated with ΔKOOS ( P < .05). Proteomic analysis showed that differentially expressed proteins integrin-linked kinase ( r = −0.50; P < .05), and glutathione peroxidase 1 ( r = −0.55; P < .01) negatively correlated with ΔKOOS Pain ( P < .05), whereas cathepsin G ( r = 0.51; P < .05), and calprotectin subunit ( r = 0.65; P < .01) were positively correlated with ΔKOOS Pain ( P < .05) (* P < .05, ** P < 0.01). Conclusion: These findings suggest that some cellular and protein biomarkers may potentially be used as therapeutic targets and predictive markers for PRP success, guiding personalized therapeutic strategies. However, these targets must be further validated for knee OA in future studies.

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