Universität zu Köln

Reichel, Christian, Gmeiner, Guenter and Thevis, Mario (2017). Antibody-based strategies for the detection of Luspatercept (ACE-536) in human serum. Drug Test. Anal., 9 (11-12). S. 1721 - 1731. HOBOKEN: WILEY. ISSN 1942-7611

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Abstract

Luspatercept (ACE-536, ACVR2B-Fc), a fusion protein consisting of the extracellular domain of ActRIIB receptor and the Fc-part of human immunoglobulin G1 (IgG1), is currently under clinical development (Phase III). It stimulates the formation of red blood cells and hence may be misused by athletes for doping purposes in the future. Several antibody-based strategies for the detection of Luspatercept and other ACVR2B-Fc fusion proteins in human serumwere evaluated (ELISA; IEF-, SDS-, and SAR-PAGE followed by Western blotting; immunoprecipitation). Two methods led to useful results: a commercial soluble ACTR-IIB ELISA, which also detected Luspatercept and other ACVR2B-Fc's, but showed no cross-reactivity with Sotatercept/ACVR2A-Fc's. The ELISA might be applied as fast screening tool (100 mu L serum; limit of detection (LOD) ca 15.6 ng/mL). The second method uses a polyclonal ACVR2B-antibody for immunoprecipitation followed by SAR-PAGE and Western blotting with a monoclonal detection antibody (50 mu L serum; LOD ca 1.0 ng/mL). It can be used for initial as well as for confirmatory testing. Due to the high doses (mg/kg) and long serum half-life of Luspatercept, both strategies may be useful in anti-doping control in the future. Copyright (c) 2017 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Reichel, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Gmeiner, Guenter UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-211810
DOI:	10.1002/dta.2302
Journal or Publication Title:	Drug Test. Anal.
Volume:	9
Number:	11-12
Page Range:	S. 1721 - 1731
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1942-7611
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RATIO MASS-SPECTROMETRY; URINARY STEROIDS; DOPING CONTROL; AMINO-ACIDS; MUSCLE; AICAR; ACTIVATION; MISUSE; SPORT; AMPK Multiple languages Biochemical Research Methods; Chemistry, Analytical; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21181