Myostatin inhibitors in sports drug testing: Detection of myostatin-neutralizing antibodies in plasma/serum by affinity purification and Western blotting

Proteomics Clin Appl. 2016 Feb;10(2):195-205. doi: 10.1002/prca.201500043. Epub 2015 Oct 23.

Abstract

Purpose: Myostatin is a key regulator of skeletal muscle growth and inhibition of its signaling pathway results in an increased muscle mass and function. The aim of this study was to develop a qualitative detection assay for myostatin-neutralizing antibodies for doping control purposes by using immunological approaches.

Experimental design: To detect different types of myostatin-neutralizing antibodies irrespective of their amino acid sequence, an immunological assay specific for antibodies directed against myostatin and having a human Fc domain was established. Affinity purification and Western blotting strategies were combined to allow extracting and identifying relevant analytes from 200 μL of plasma/serum in a non-targeted approach. The assay was characterized regarding specificity, linearity, precision, robustness, and recovery.

Results: The assay was found to be highly specific, robust, and linear from 0.1 to 1 μg/mL. The precision was successfully specified at three different concentrations and the recovery of the affinity purification was 58%.

Conclusions and clinical relevance: Within this study, an immunological detection assay for myostatin-neutralizing antibodies present in plasma/serum specimens was developed and successfully characterized. The presented approach can easily be modified to include other therapeutic antibodies and serves as proof-of-concept for the detection of antibody-based myostatin inhibitors in doping control samples.

Keywords: Affinity purification; Doping; Myostatin; Therapeutic antibodies; Western blotting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / blood*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / isolation & purification*
  • Blotting, Western*
  • Chromatography, Affinity
  • Doping in Sports*
  • Humans
  • Myostatin / antagonists & inhibitors*
  • Myostatin / immunology*
  • Performance-Enhancing Substances / blood*
  • Performance-Enhancing Substances / immunology
  • Performance-Enhancing Substances / isolation & purification*

Substances

  • Antibodies, Neutralizing
  • MSTN protein, human
  • Myostatin
  • Performance-Enhancing Substances