title: Glyco-engineering for the production of recombinant IgA1 with distinct mucin-type O-glycans in plants.
abstract: IgA nephropathy (IgAN) is a common autoimmune disease that is characterized by formation and deposition of IgA1-containing immune complexes frequently leading to end-stage kidney disease. The IgA1 in these immune complexes carries aberrantly glycosylated O-glycans. In circulating IgA1 these galactose-deficient mucin-type O-glycans are bound by autoantibodies and thus, contribute to immune complex formation and pathogenesis. Even though the disease is associated with the overproduction of aberrant O-glycans on IgA1, specific structure-function-studies of mucin-type O-glycans are limited. Compared to other expression hosts, plants offer the opportunity for de novo synthesis of O-glycans on recombinant glycoproteins as they are lacking the mammalian O-glycosylation pathway. Recently, we demonstrated that Nicotiana benthamiana are suitable for the generation of distinct O-glycans on recombinant IgA1. Here, we expand our engineering repertoire by in planta generation of galactose-deficient and α2,6-sialylated O-glycans which are the prevailing glycans detected on IgA1 from patients with IgAN.
authors.affiliation: a Department of Applied Genetics and Cell Biology , University of Natural Resources and Life Sciences , Vienna , Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Dicker
authors.affiliation: b Department of Chemistry , University of Natural Resources and Life Sciences , Vienna , Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Maresch
authors.affiliation: a Department of Applied Genetics and Cell Biology , University of Natural Resources and Life Sciences , Vienna , Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Strasser
mesh_terms: D000936:Antigen-Antibody Complex / Q000096:biosynthesis / Q000276:immunology; D005690:Galactose / Q000378:metabolism; D005786:Gene Expression Regulation; D005818:Genetic Engineering / Q000379:methods*; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D009077:Mucins / Q000096:biosynthesis*; D011134:Polysaccharides / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis*; D014026:Nicotiana / Q000235:genetics / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D009077:Mucins; D011134:Polysaccharides; D011994:Recombinant Proteins; D005690:Galactose
keywords: IgA nephropathy; O-glycan; glyco-engineering; glycosylation; immunoglobulin A; post-translational modification; recombinant protein