Dépôt numérique

Detection of activin receptor type IIA and IIB-Fc fusion proteins by automated capillary immunoassay

Desharnais, Philippe et Naud, Jean-François ORCID logoORCID: https://orcid.org/0000-0001-8667-111X (2022). Detection of activin receptor type IIA and IIB-Fc fusion proteins by automated capillary immunoassay Drug Testing and Analysis , vol. 14 , nº 11-12. pp. 1938-1951. DOI: 10.1002/dta.3378.

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Activin receptor type IIA and type IIB fusion protein have been designed to sequester circulating molecules of the TGF-β superfamily and inactivate their actions. Members of this superfamily have been reported as essential regulators of erythropoiesis by triggering the formation of activated ternary complexes containing different combinations of type I and type II receptors which can limit RBC production by accelerating erythroid differentiation and inhibiting erythroid progenitor expansion. The recent approval of Luspatercept for the treatment of anemia associated to transfusion-dependent MDS and Beta-thalassemia in afflicted patients means that it can now pose a real threat of being abuse in sport for its ability to stimulate erythropoiesis. Several methods for the detection of these molecules in blood have been proposed for the purpose of sport antidoping control. Here we propose the detection of the ActRIIA-Fc and ActRIIB-Fc fusion proteins by automated capillary Western immunoassay (Simple Western). The use of these immunoassays for the detection of protein targets has become widespread in the recent years. The work presented here demonstrates that this methodology enables a versatile, rapid, and sensitive detection of activin ligand traps in blood samples, either plasma, serum or DBS. Preliminary results indicate that detection in urine samples is also possible. The option to use different antibodies allows the possibility to use this method as an initial testing procedure as well as a confirmation procedure. Finally, results coming from an administration study confirm that the method is suitable for routine analysis.

Type de document: Article
Mots-clés libres: Luspatercept; Sotatercept; antidoping; capillary immunoassay; detection.
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 08 déc. 2023 22:01
Dernière modification: 08 déc. 2023 22:01
URI: https://espace.inrs.ca/id/eprint/13366

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