title: Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment.
abstract: The pathogenic role of immunoglobulin E (IgE) antibodies in triggering and maintaining allergic inflammation in response to allergens is due to the binding of multivalent allergens to allergen-specific IgEs on sensitized effector cells. These interactions trigger effector cell activation, resulting in release of potent inflammatory mediators, recruitment of inflammatory cells, antigen presentation, and production of allergen-specific antibody responses. Since its discovery in the 1960s, the central role of IgE in allergic disease has been intensively studied, placing IgE and its functions at the heart of therapeutic efforts for the treatment of allergies. Here, we provide an overview of the nature, roles, and significance of IgE antibodies in allergic diseases, infections, and inflammation and the utility of antibodies as therapies. We place special emphasis on allergen-IgE-Fcε receptor complexes in the context of allergic and inflammatory diseases and describe strategies, including monoclonal antibodies, aimed at interrupting these complexes. Of clinical significance, one antibody, omalizumab, is presently in clinical use and works by preventing formation of IgE-Fcε receptor interactions. Active immunotherapy approaches with allergens and allergen derivatives have also demonstrated clinical benefits for patients with allergic diseases. These treatments are strongly associated with serum increases of IgE-neutralizing antibodies and feature a notable redirection of humoral responses towards production of antibodies of the IgG4 subclass in patients receiving immunotherapies. Lastly, we provide a new perspective on the rise of recombinant antibodies of the IgE class recognizing tumor-associated antigens, and we discuss the potential utility of tumor antigen-specific IgE antibodies to direct potent IgE-driven immune responses against tumors.
authors.affiliation: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Karagiannis
authors.affiliation: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Karagiannis
authors.affiliation: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Debra H
authors.initials: DH
authors.lastname: Josephs
authors.affiliation: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Saul
authors.affiliation: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Gilbert
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Division of Asthma, Allergy, and Lung Biology, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom.
authors.forename: Nadine
authors.initials: N
authors.lastname: Upton
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Division of Asthma, Allergy, and Lung Biology, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Gould