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Allergy Dec 2023Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases often characterized by the presence of pathogenic autoreactive... (Review)
Review
Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases often characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro-inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils, and other types of FcεRI-bearing cells and may play a role in promoting autoantibody production and other pro-inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.
Topics: Humans; Immunoglobulin E; Autoimmune Diseases; Basophils; Omalizumab; Autoimmunity; Receptors, IgE
PubMed: 37555488
DOI: 10.1111/all.15843 -
Allergy Oct 2020About 20 years after the identification of immunoglobulin E (IgE) and its key role in allergic hypersensitivity reactions against normally harmless substances,... (Review)
Review
About 20 years after the identification of immunoglobulin E (IgE) and its key role in allergic hypersensitivity reactions against normally harmless substances, scientists have started inventing strategies to block its pathophysiological activity in 1986. The initial concept of specific IgE targeting through the use of anti-IgE antibodies has gained a lot of momentum and within a few years independent research groups have reported successful generation of first murine monoclonal anti-IgE antibodies. Subsequent generation of optimized chimeric and humanized versions of these antibodies has paved the way for the development of therapeutic anti-IgE biologicals as we know them today. With omalizumab, there is currently still only one therapeutic anti-IgE antibody approved for the treatment of allergic conditions. Since its application is limited to the treatment of moderate-to-severe persistent asthma and chronic spontaneous urticaria, major efforts have been undertaken to develop alternative anti-IgE biologicals that could potentially be used in a broader spectrum of allergic diseases. Several new drug candidates have been generated and are currently assessed in pre-clinical studies or clinical trials. In this review, we highlight the molecular properties of past and present anti-IgE biologicals and suggest concepts that might improve treatment efficacy of future drug candidates.
Topics: Animals; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Products; Humans; Mice; Omalizumab
PubMed: 32249957
DOI: 10.1111/all.14308 -
International Journal of Pediatric... Dec 2019To review the efficacy of anti-IgE therapy in allergic rhinitis (AR). (Review)
Review
OBJECTIVES
To review the efficacy of anti-IgE therapy in allergic rhinitis (AR).
METHODS
Literature search was performed using the PubMed and Proquest Central databases at Kırıkkale University Library.
RESULTS
Although the skin prick testing in patients suffering from AR is positive (indicating that antigen-specific Immunoglobulin E has been produced), there is no association with overall circulating IgE levels. Correlation was lacking between circulating IgE level and either skin prick tests or laboratory testing for specific IgE. Omalizumab binds to uncomplexed IgE in man more avidly than does Fc-epsilon. The effect of omalizumab is to lower the level of IgE and downgrade production of FceRI receptors (which bind IgE) in mast cells and basophils, causing less mast cell recruitment and responsivity and thus diminishing eosinophilic infiltration and activation. Anti-IgE therapy through omalizumab may shorten the lifetime of mast cells and causes dendritic cells to downgrade their production of FcεRI. There are reports indicating benefit from omalizumab in managing food allergies, nasal polyp formation, essential anaphylaxis, AR, venom allergy and eczema. Omalizumab acts to lessen circulating IgE levels, whilst reducing production of FceRI by mast cells and basophils. The fact that omalizumab influences how eosinophils respond may be down to disruption of the antigen-IgE-mast cell interactions, with mast cells being recruited at lower levels and thus chemotactic eosinophilic recruitment via cytokines being greatly reduced. Omalizumab has the effect in cases of perennial AR of blocking the increased eosinophilic recruitment and tissue infiltration initiated by seasonal antigens. Likewise, in omalizumab-treated cases, circulating unbound IgE levels showed significant decreases. For patients with perennial AR, the average daily nasal severity score was significantly reduced where omalizumab was administered, compared to placebo.
CONCLUSION
Omalizumab has efficacy in ameliorating symptoms and reduces the necessity for additional medication in both seasonal and perennial allergic rhinitis.
Topics: Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Basophils; Eosinophils; Humans; Immunoglobulin E; Immunotherapy; Omalizumab; Rhinitis, Allergic
PubMed: 31526939
DOI: 10.1016/j.ijporl.2019.109674 -
The Journal of Allergy and Clinical... Feb 2020
Topics: Cohort Studies; Female; Humans; Omalizumab; Pregnancy; Pregnancy Outcome; Premature Birth; Registries
PubMed: 31778706
DOI: 10.1016/j.jaci.2019.11.018 -
Current Opinion in Allergy and Clinical... Dec 2021To review the most relevant studies in the advancing field of omalizumab in allergen immunotherapy. (Review)
Review
PURPOSE OF REVIEW
To review the most relevant studies in the advancing field of omalizumab in allergen immunotherapy.
RECENT FINDINGS
Omalizumab has been used in combination with inhalant, venom, and food allergen immunotherapy. These studies suggest that omalizumab can decrease the time required to reach maintenance dosing and adverse events. However, severe adverse events do still occur. Limited long-term data suggests that there is a risk for increased reactivity after stopping omalizumab.
SUMMARY
Omalizumab in conjunction with immunotherapy has shown promising results for the treatment of allergic rhinitis, venom hypersensitivity, and food allergy, especially in the reduction of adverse events. Larger randomized, placebo-controlled trials are needed to better understand optimal dosing and duration, cost--benefit analysis, ideal patients, and long-term benefits. This combination therapy has the potential to improve treatment, particularly for high-risk patients.
Topics: Allergens; Desensitization, Immunologic; Food Hypersensitivity; Humans; Immunotherapy; Omalizumab; Rhinitis, Allergic; Venoms
PubMed: 34419967
DOI: 10.1097/ACI.0000000000000781 -
Parasite Immunology Feb 2023Human fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic... (Review)
Review
Human fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic pathogens are capable of morphotype switching, they present unique challenges both for drug development and the immunological response. Whilst current antifungal therapies are limited to the orally available triazoles, intravenous echonocandins and polyenes, and flucytosine and terbinafine, there has been recent significant progress in the antifungal armamentorium with ibrexafungerp, a novel orally available terpanoid that inhibits 1,3-beta-D-glucan-approved by Food and Drug Administration in 2021, and fosmanogepix, an orally available pro-drug of manogepix, which targets glycosylphosphatidylinositol-anchored protein maturation entering Phase 3 studies for candidaemia. A number of further candidates are in development. There has been significant use of existing immunotherapies such as recombinant interferon-γ and G-CSF for fungal disease in immunocompromised patients, and there are emerging opportunities for monoclonal antibodies targeting TH2 inflammation. Omalizumab, an anti-IgE monoclonal antibody in asthma, is now used routinely for the treatment of allergic bronchopulmonary aspergillosis, and further agents targeting IL-4 and IL-5 are being evaluated. In addition, T-cell CAR therapy is showing early promise for fungal disease. Thus, we are likely to see rapid advances to our approach to the management of fungal disease in the near future.
Topics: United States; Humans; Antifungal Agents; Mycoses; Omalizumab; Asthma; Immunotherapy
PubMed: 36403106
DOI: 10.1111/pim.12960 -
Current Opinion in Allergy and Clinical... Jun 2023A better understanding of the most recent scientific literature in the use of biological therapy in the treatment of patients with IgE-mediated food allergy. (Meta-Analysis)
Meta-Analysis
PURPOSE OF REVIEW
A better understanding of the most recent scientific literature in the use of biological therapy in the treatment of patients with IgE-mediated food allergy.
RECENT FINDINGS
A systematic review and meta-analysis demonstrated safety and effectiveness of omalizumab in the treatment of food allergy. The findings support the potential use of omalizumab as a monotherapy or as an adjunct to oral immunotherapy in IgE-mediated cow's milk allergy. The potential use of other biologics in the management of food allergy is subject of speculation.
SUMMARY
Different biological therapies are under evaluation for food allergic patients. The advance in literature will guide for a personalized treatment in the near future. However, additional research is needed to better understand the best candidate for each treatment, the optimal dose and timing.
Topics: Animals; Female; Cattle; Humans; Omalizumab; Biological Products; Immunoglobulin E; Food Hypersensitivity; Milk Hypersensitivity; Desensitization, Immunologic
PubMed: 37185824
DOI: 10.1097/ACI.0000000000000900 -
Expert Opinion on Biological Therapy Sep 2021In recent years, the advent of immunotherapy has remarkably improved the management of IgE-mediated food allergy. However, some barriers still exist. Therefore, the... (Review)
Review
In recent years, the advent of immunotherapy has remarkably improved the management of IgE-mediated food allergy. However, some barriers still exist. Therefore, the effort of researchers aims to investigate new perspectives in the field of non-allergen specific therapy, also based on the current knowledge of the pathogenesis of this disease. This review aims to focus on the role of biologics as a treatment option in patients with IgE-mediated food allergy. These agents are characterized by their ability to inactivate the Th2 pro-inflammatory pathways. Biologics can be used both alone and in association with immunotherapy. Monoclonal antibodies targeting IgE, the IL-4/IL-13 axis, IL-5, and alarmins have been proposed and investigated for treating food allergy. The clinical efficacy and safety of biologics have been demonstrated in several preclinical studies and randomized controlled trials. Future studies are still required to address current unmet needs, including the identification of the optimal dose to be used by ensuring the effectiveness of therapy.
Topics: Antibodies, Monoclonal; Biological Products; Food Hypersensitivity; Humans; Immunotherapy; Omalizumab
PubMed: 33733975
DOI: 10.1080/14712598.2021.1904888 -
International Journal of Molecular... May 2024Despite advancements in vaccinology, there is currently no effective anti-HIV vaccine. One strategy under investigation is based on the identification of epitopes...
Despite advancements in vaccinology, there is currently no effective anti-HIV vaccine. One strategy under investigation is based on the identification of epitopes recognized by broadly neutralizing antibodies to include in vaccine preparation. Taking into account the benefits of anti-idiotype molecules and the diverse biological attributes of different antibody formats, our aim was to identify the most immunogenic antibody format. This format could serve as a foundational element for the development of an oligo-polyclonal anti-idiotype vaccine against HIV-1. For our investigation, we anchored our study on an established b12 anti-idiotype, referred to as P1, and proposed four distinct formats: two single chains and two minibodies, both in two different orientations. For a deeper characterization of these molecules, we used immunoinformatic tools and tested them on rabbits. Our studies have revealed that a particular minibody conformation, MbVHVL, emerges as the most promising candidate. It demonstrates a significant binding affinity with b12 and elicits a humoral anti-HIV-1 response in rabbits similar to the Fab format. This study marks the first instance where the minibody format has been shown to provoke a humoral response against a pathogen. Furthermore, this format presents biological advantages over the Fab format, including bivalency and being encoded by a monocistronic gene, making it better suited for the development of RNA-based vaccines.
Topics: Animals; Rabbits; HIV Antibodies; HIV-1; Immunity, Humoral; Antibodies, Anti-Idiotypic; AIDS Vaccines; HIV Infections; Humans; Antibodies, Neutralizing; Computer Simulation; Epitopes
PubMed: 38891926
DOI: 10.3390/ijms25115737 -
Skinmed 2021The exposure to cold can induce the development of wheals and angioedema in a group of susceptible individuals: this phenomenon is largely known as cold-induced...
The exposure to cold can induce the development of wheals and angioedema in a group of susceptible individuals: this phenomenon is largely known as cold-induced urticaria. The pathogenesis of cold-induced urticaria is not yet understood, although both autoallergens and immunoglobulin (Ig)E-mediated autoimmunity are presumed to be involved. Flares of cold-induced urticaria might depend on the release of histamine and other pro-inflammatory mediators, such as Interleukin (IL)-1, which is the predominating stakeholder of cryopyrin-associated periodic syndrome, a genetic disease characterized by cold-induced skin manifestations, including urticaria-like rashes. The majority of occurrence of cold-induced urticaria in children is idiopathic, but forms secondary to systemic conditions have been also reported. Primarily, the diagnosis remains a clinical process based on the history of patient, cold stimulation tests, and a few laboratory results, which could be useful for the excluding any underlying disorders. The general rules to manage cold-induced urticaria in children can be summarized with cold avoidance, treatment with nonsedating antihistamines, and the anti-IgE monoclonal antibody omalizumab in selected patients. Familiar forms of cryopyrin-associated periodic syndrome could be prevented even in pediatric patients from the selective IL-1 blockade. Injectable epinephrine must be immediately used to manage the potential life-threatening manifestations occurring in a minority of children with cold-induced urticaria.
Topics: Angioedema; Child; Epinephrine; Humans; Omalizumab; Urticaria
PubMed: 34861913
DOI: No ID Found