title: Immunoglobulin A: magic bullet or Trojan horse?
abstract: BACKGROUND
  Neutrophils participate in the first line of defense by executing several killing mechanisms, including phagocytosis, degranulation and the release of neutrophil extracellular traps. Additionally, they can orchestrate the adaptive immune system by secreting cytokines and chemokines. Opsonization with antibodies aids in the recognition of pathogens, via binding to Fc receptors on the neutrophil surface. Immunoglobulin A (IgA) is the most abundant antibody at mucosal sites and has multiple functions in homeostasis and immunity. Neutrophils and IgA can interact via the IgA Fc receptor Fc?RI (CD89), leading to pro- or anti-inflammatory responses.
  
  
  OBJECTIVE
  The aim of this review is to give a concise overview of the interplay between IgA, Fc?RI and neutrophils and to explore potential therapies for autoimmune diseases and cancer.
  
  
  RESULTS
  Crosslinking of FcαRI by IgA-immune complexes yields potent neutrophil activation and pro-inflammatory effector functions, including the recruitment of neutrophils. This can lead to neutrophil accumulation and tissue destruction during IgA-autoantibody mediated diseases. Conversely, for cancer treatment, the myriad of powerful neutrophil effector functions after targeting FcαRI may contribute to effective immunotherapy.
  
  
  CONCLUSIONS
  By interfering with or actively promoting the interaction between IgA and FcαRI, therapies for multiple maladies could be developed.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Marieke H
authors.initials: MH
authors.lastname: Heineke
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands.|Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Egmond
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000502:physiology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D005544:Forecasting; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007070:Immunoglobulin A / Q000502:physiology*; D007167:Immunotherapy / Q000379:methods; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C036832:Fc(alpha) receptor; C045281:IgA receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc
keywords: Autoimmune disease; CD89; FcαRI; cancer; immunoglobulin A; neutrophil