Treatment with recombinant human bone morphogenetic protein 7 leads to a transient induction of neutralizing autoantibodies in a subset of patients

Publication date: Available online 3 August 2016 Source:BBA Clinical Author(s): Andrea Schuette, Arash Moghaddam, Petra Seemann, Georg N. Duda, Gerhard Schmidmaier, Lutz Schomburg Background Recombinant human bone morphogenetic protein 7 (rhBMP7) is applied for treatment of bone fractures, especially tibial non-unions. Its application may induce autoantibodies (aAB) affecting the targeted and endogenous signaling pathways and in turn negatively impact treatment efficacy. Methods Novel and sensitive assays for the quantification of BMP7-aAB and BMP2-aAB were established and used to analyze serum samples from healthy controls (n =100 men, n=100 women) and patients with long bone fracture (n =265) treated or not with rhBMP7. Sera from three to nine time points per patient were available and enabled the evaluation of aAB over a time course of up to one year. Functional activity of the BMP-aAB was tested with a BMP-responsive cell-based reporter assay. Consolidation of the fracture was evaluated as clinical outcome potentially affected by BMP7-aAB. Results Prevalence of BMP7-aAB and BMP2-aAB were 1–2.5% in non-treated patients or healthy controls. The rhBMP7 treatment induced a transient increase in BMP7-aAB in a subset of patients, returning to non-detectable levels within six months. IgG from BMP7-aAB positive sera inhibited dose dependently the BMP7-reporter gene activity, whereas control sera were without effect. Successful consolidation of the fracture was observe...
Source: BBA Clinical - Category: Biochemistry Source Type: research