Multimodal immune profiling of peripheral blood to predict the response to intra-articular autologous blood-derived orthobiologic treatment in patients with knee osteoarthritis.

OBJECTIVE

Innate and adaptive immunity, oxidative stress and altered bone remodeling have been implicated in the pathogenesis of knee osteoarthritis (OA). Intra-articular blood-derived orthobiologic treatments (broadly defined within the umbrella term platelet-rich plasma - PRP) represent a conservative therapeutic approach, yet reliable predictors of treatment response remain elusive. Multimodal profiling of peripheral blood may help identify responders to PRP.

METHODS

Patients aged 40-70 years with Kellgren-Lawrence grade 2-3 knee OA, no history of inflammatory arthritis, and a BMI < 40 kg/m² received a single knee PRP injection. Prior to treatment, peripheral blood was collected to assess gene and protein expression of inflammatory and bone remodeling molecules, and antioxidant capacity. Multiparametric flow cytometry with cluster analysis was also performed to identify immune cell subsets. Treatment response was assessed six months post-injection using the WOMAC questionnaire.

RESULTS

Among 55 patients, 45 were responders, with no differences in age, sex, or disease duration compared to non-responders. Responders exhibited a higher peripheral blood inflammatory signature, including upregulation of IL-1, IL-6, and TNF signaling pathways, increased RANKL and SFRP3 expression. Serum levels of ascorbic acid and 4-hydroxynonenal were more elevated in PRP responders. Flow cytometry identified populations of CD4⁺ T cells (expressing HLA-DR, CD95, and PD-1) and CD8⁺ T cells (expressing CD25 and CCR7), which were differentially represented between PRP responders and non-responders.

CONCLUSIONS

Early response to autologous blood-derived orthobiologic injections could be associated with specific inflammatory and oxidative stress markers and distinct peripheral blood T cell phenotypes of patients undergoing treatment. Further studies are warranted to validate these findings in larger cohorts at extended follow-up timepoints.