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

Abstract

BackgroundThere 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.MethodsEleven 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.ResultsThe WBC concentration in APS was significantly (p < 0.05) and strongly (R2 > 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.ConclusionsThe 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)Electronic supplementary materialThe online version of this article (doi:10.1186/s40634-016-0043-7) contains supplementary material, which is available to authorized users.

Human blood‐based anti‐inflammatory solution inhibits osteoarthritis progression in a meniscal‐tear rat study

“…37 Alternatively, there has not been any correlation between the concentration of WBCs in APS and inflammatory cytokines. 17 In this meniscal-tear study with APS, no adverse events were reported. Gait analysis (Fig.…”

“…Subjects with IL-1ra:IL-1b ratios greater than 1000 or with high WBC concentrations in their APS were more likely to be Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) high pain responders. [17][18][19] These results support the use of APS as a method of directly interfering with the inflammatory molecular pathways causing OA, reducing pain and improving function simultaneously.…”

“…Also, there were no AE that were related to the device. There were minor AE related to the injection procedure, including injection site discomfort (1/11), injection site joint pain (1/11), and procedural nausea (1/11), which resolved quickly and did not require treatment . In a randomized and controlled equine and canine trials there were no complications seen with injections of APS or saline.…”

“…Now the same research group that has reported that WBCs contribute inflammatory cytokines has demonstrated that WBC‐rich cBMA contains high concentrations of IL‐1ra and a low IL‐1ra/IL‐1β ratio . Previous testing has demonstrated that there is strong correlation between increasing WBC concentration in APS and increasing concentrations of IL‐1ra . WBCs naturally contain high concentrations of IL‐1ra in the body .…”

“…36 Previous testing has demonstrated that there is strong correlation between increasing WBC concentration in APS and increasing concentrations of IL-1ra. 17 WBCs naturally contain high concentrations of IL-1ra in the body. 37 Alternatively, there has not been any correlation between the concentration of WBCs in APS and inflammatory cytokines.…”