title: C1 Inhibitor as a glycoprotein: The influence of polysaccharides on its function and autoantibody target.
abstract: C1 Inhibitor (C1Inh), a member of the Serine proteinase inhibitor family, is the most heavily glycosylated plasma protein. This work investigated the impact of C1Inh glycosylation on its function regarding protease targets and autoantibody binding. C1Inh deglycosylation was found to affect its function with O-linked polysaccharides, but not with N-linked polysaccharides, in controlling the contact phase but not C1s target, thus indicating the N-terminal domain's involvement in C1Inh function. Instructive samples demonstrated that O-deglycosylation strongly suppressed autoantibody binding, suggesting the polysaccharide motif is an antibody target. The autoantibodies did not directly affect C1Inh function.
authors.affiliation: KininX SAS, Grenoble, France. Electronic address: arije.ghannam@kininx.com.
authors.forename: Arije
authors.initials: A
authors.lastname: Ghannam
authors.affiliation: KininX SAS, Grenoble, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Sellier
authors.affiliation: Internal medicine department, Saint Antoine Hospital, AP-HP, DHU i2B, Paris 6 University, Paris, France; Centre de Référence des Angioedèmes CREAK, CHU Grenoble, CHU Angers and AP-HP, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fain
authors.affiliation: Centre de Référence des Angioedèmes CREAK, CHU Grenoble, CHU Angers and AP-HP, Paris, France; L'UNAM Université, Dermatology department, University Hospital, Angers, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.affiliation: Centre de Référence des Angioedèmes CREAK, CHU Grenoble, CHU Angers and AP-HP, Paris, France; CHU Grenoble, Laboratoire d'Immunologie, Grenoble, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Ponard
authors.affiliation: Centre de Référence des Angioedèmes CREAK, CHU Grenoble, CHU Angers and AP-HP, Paris, France; Université Joseph Fourier, GREPI EA-UJF 7408, Grenoble, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Drouet
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D050718:Complement C1 Inhibitor Protein; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D056829:Hereditary Angioedema Types I and II / Q000378:metabolism*; D006801:Humans; D011134:Polysaccharides / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D006023:Glycoproteins; D011134:Polysaccharides; C469952:SERPING1 protein, human
keywords: Acquired angioedema; C1 inhibitor; Contact phase; Glycosylation