White blood cell concentration correlates with increased concentrations of IL-1ra and improvement in WOMAC pain scores in an open-label safety study of autologous protein solution.

BACKGROUND: There has been debate on which blood components should be included in autologous therapies. Autologous Protein Solution (APS) is a unique blood-derived therapy composed of concentrated white blood cells, platelets, and plasma to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors to potentially address osteoarthritis. The primary aim of the exploratory secondary analysis was to identify characteristics of an Autologous Protein Solution (APS) that may correlate with improved Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and OMERACT-OARSI responder status after treatment of subjects with an intra-articular injection of APS. METHODS: Eleven subjects were enrolled in a pilot study of a single intra-articular injection of APS in subjects with knee osteoarthritis. Two APS kits were processed per patient. The output of the first APS kit was injected intra-articularly. White blood cell (WBC) and cytokine concentrations were measured from the output of the second APS kit. WOMAC surveys were completed at baseline and at follow up visits. Linear regression analyses were performed on the blood components of APS with subject outcomes. Anderson-Darling analysis was used to determine whether the cytokine concentrations in whole blood and APS had a normal distribution. Either paired t-test analyses or Wilcoxon signed-rank analyses were performed for normal and non-parametrically distributed data, respectively. RESULTS: The WBC concentration in APS was significantly (p < 0.05) and strongly (R(2) > 0.7) correlated with IL-1ra in APS but not significantly correlated with IL-1β. The ratio of IL-1ra to IL-1β in APS was significantly correlated with improved WOMAC pain scores one week and six months post-injection. 85.7 % of subjects whose APS had a IL-1ra:IL-1β ratio greater than 1000 or a WBC count greater than 30 k/μl were OMERACT-OARSI responders six months post-injection. CONCLUSIONS: The correlations between the IL-1ra:IL-1β ratio and WBC concentration in a subject's APS and their WOMAC pain scores and classification as OMERACT-OARSI responders suggest the potential utility of these characteristics as diagnostic markers. Additional studies are ongoing to determine whether APS is safe and effective and to further evaluate the relationship between APS composition and clinical outcomes. TRIAL REGISTRATION: ( NCT01773226 ).