No interactions between heparin and atacicept, an antagonist of B cell survival cytokines

• DOI: 10.1111/bph.14811
• Publication Date: 2019-07-29T11:55:57Z
• Authors: Christine Kowalcz...; Daniela Willen; Laure Willen; Michaela Golob; Sonia Schuepbach‐...; Benjamin Peter; Mahya Eslami; Michele Vigolo; Hervé Broly; Eileen Samy; Özkan Yalkinoglu; Pascal Schneider
• Keywords: Proinflammatory cytokine

The TNF family ligands, B cell activating factor of the (BAFF, also known as lymphocyte stimulator, BLyS) and a proliferation-inducing ligand (APRIL), share transmembrane activator calcium-modulator cyclophilin (CAML)-interactor (TACI) one their common receptors. Atacicept, chimeric recombinant TACI/IgG1-Fc fusion protein, inhibits both ligands. TACI APRIL bind to proteoglycans heparin that is structurally related proteoglycans. It unknown whether portion contained in atacicept can directly proteoglycans, or indirectly via APRIL, this could interfere with anti-coagulant properties heparin.Binding proteoglycan-positive cells was measured by FACS. Activities were activated Xa inhibition cell-based assays. Effects on circulating monitored mice.Atacicept did not cells, but when complexed do so APRIL. Multimers obtained after exposure cysteine BAFF 60-mer bound Atacicept alone, complex multimeric form activity vitro. Conversely, influence change levels atacicept.Lack detectable interference APRIL-bound free makes it unlikely at therapeutic doses will function vivo.