title: Innate immune response and implant loosening: Interferon gamma is inversely associated with early migration of total knee prostheses.
abstract: To allow prediction of the risk of loosening prior to surgery, we investigated the relationship between innate immune cytokine response via TLR2 stimulation and early migration of six different knee prostheses using RSA (radiostereometry). This study included 114 patients of a prospective RSA-cohort who received a total knee arthroplasty. Whole blood cytokine responses were obtained by ex vivo stimulation with tripalmitoyl-S-glycerylcysteine (Pam3Cys-SK4) for assessment of the TLR2 immune response. Early migration was calculated using the maximum total point motion (MTPM) 1 year post surgery. Principal component analysis (PCA) was applied to the cytokine data to reduce the correlated data of individual cytokines and identified two components. Subsequently, linear mixed model analyses were applied with adjustments for gender, age, BMI, time-to-blood sampling, and prosthesis type. Component 1, consisting of IFNγ, IL-12p40, IL-10, IL-1β, TNFα, and IL-6, showed a significant inverse association (β = -0.128; p = 0.041) with MTPM. Further analysis showed that IFNγ (β = -0.161, p = 0.008) had the highest contribution to this association and is particularly found in patients receiving another prosthesis than Nexgen (β = -0.239; p < 0.001). In conclusion, patients with high levels of IFNγ upon stimulation of TLR2 are at lower risk of early migration of their knee prosthesis.
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Monique A E
authors.initials: MA
authors.lastname: Schoeman
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Bart G
authors.initials: BG
authors.lastname: Pijls
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Oostlander
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johan C
authors.initials: JC
authors.lastname: Keurentjes
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.|Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Delft, The Netherlands.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Valstar
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rob G H H
authors.initials: RG
authors.lastname: Nelissen
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meulenbelt
mesh_terms: D000368:Aged; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D011475:Prosthesis Failure / Q000209:etiology*; D059869:Radiostereometric Analysis
chemical_list: D055666:Lipopeptides; C560312:Pam2CSK4 lipopeptide; D007371:Interferon-gamma
keywords: IFNγ; TLR2; aseptic loosening; migration