Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

• Published in: The New England journal of medicine Vol. 370; no. 17; pp. 1615 - 1625
• Main Authors: Sadat, Mohammed A, Moir, Susan, Chun, Tae-Wook, Lusso, Paolo, Kaplan, Gerardo, Wolfe, Lynne, Memoli, Matthew J, He, Miao, Vega, Hugo, Kim, Leo J.Y, Huang, Yan, Hussein, Nadia, Nievas, Elma, Mitchell, Raquel, Garofalo, Mary, Louie, Aaron, Ireland, Derek C, Grunes, Claire, Cimbro, Raffaello, Patel, Vyomesh, Holzapfel, Genevieve, Salahuddin, Daniel, Bristol, Tyler, Adams, David, Marciano, Beatriz E, Hegde, Madhuri, Li, Yuxing, Calvo, Katherine R, Stoddard, Jennifer, Justement, J. Shawn, Jacques, Jerome, Long Priel, Debra A, Murray, Danielle, Sun, Peter, Kuhns, Douglas B, Boerkoel, Cornelius F, Chiorini, John A, Di Pasquale, Giovanni, Verthelyi, Daniela, Rosenzweig, Sergio D
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 24.04.2014
• Series: Brief Report
• Subjects: Agammaglobulinemia - genetics; Agammaglobulinemia - immunology; alpha-Glucosidases - genetics; Antibodies, Viral - blood; Child; Congenital diseases; Congenital Disorders of Glycosylation - genetics; Congenital Disorders of Glycosylation - immunology; Congenital Disorders of Glycosylation - metabolism; Disease Resistance - genetics; Endoplasmic reticulum; Female; Glycosylation; Humans; Hypogammaglobulinemia; Immunoglobulins; Immunoglobulins - metabolism; Immunology; Male; Mannosyl-oligosaccharide glucosidase; N-glycans; Neurological complications; Phenotypes; Polysaccharides; Viral infections; Virus Diseases - immunology
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1302846

In two siblings, a congenital disorder of glycosylation (CDG-IIb) was shown to lead to severe hypogammaglobulinemia but paradoxically impaired viral replication. Most proteins, including immunoglobulins, human virus receptors, and viral-coded proteins, are post-translationally modified with sugars or sugar chains that are generically referred to as glycans. Glycans are primarily classified as N-linked or O-linked oligosaccharides, depending on whether they are bound to the amide group of asparagine (N-linked) or the hydroxyl group of serine or threonine (O-linked). Glycans are associated with protein conformation, folding, solubility, stability, half-life, and antigenicity and are the moieties recognized by glycan-binding proteins. The congenital disorders of glycosylation (CDGs) are genetic disorders affecting the N-glycosylation process. CDGs are divided into defects in the synthesis of N-glycans (CDG-I) . . .