title: The Elements Steering Pathogenesis in IgG-Mediated Alloimmune Diseases.
abstract: Alloimmune diseases can occur in pregnancy and after blood transfusions, where antibodies are formed, targeting foreign cells and tissues for destruction by myeloid cells through IgG Fc-receptors (FcγR). In pregnancy, antibodies against human blood group or platelet antigens (e.g. HPA1-a) cause life-threatening anemia or thrombocytopenia in the developing fetus or newborn. Here we discuss how both the induction of those IgG antibodies as well as the proinflammatory status of the fetus affects the effector functions through FcγR. Recent studies have found IgG-glycosylation to be important with low IgG-Fc-core fucosylation resulting in increased affinity to FcγRIIIa and FcγRIIIb and enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. The importance of these and other features, including oxidative stress and acute phase responses (C-reactive protein, CRP), will be discussed and how these features may collectively synergize resulting in elevated disease pathology in these allo-, but also autoimmune mediated diseases.
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Myrthe E
authors.initials: ME
authors.lastname: Sonneveld
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
authors.forename: C Ellen
authors.initials: CE
authors.lastname: van der Schoot
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands. G.Vidarsson@sanquin.nl.
authors.forename: Gestur
authors.identifier: 0000-0001-5621-003X
authors.initials: G
authors.lastname: Vidarsson
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D002097:C-Reactive Protein / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007154:Immune System Diseases / Q000209:etiology* / Q000378:metabolism*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011485:Protein Binding; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins
chemical_list: D002097:C-Reactive Protein; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007518:Isoantibodies; D017452:Receptors, IgG; C046179:glycosylated IgG; D006023:Glycoproteins
keywords: Alloimmune thrombocytopenia; C-reactive protein; Fc receptors; Glycosylation; IgG