GATA-2–deficient mast cells limit IgE-mediated immediate hypersensitivity reactions in human subjects

Abstract Background Olaparib is a revolutionary treatment for patients with ovarian and breast cancer. Currently, there is no established 1-day drug desensitization protocol for patients with olaparib type-1 hypersensitivity reactions despite well documented IgE-mediated adverse reactions occurring with olaparib. Case presentation We report a 58-year-old female with immediate, reproducible IgE-mediated adverse reactions to olaparib tablets with implementation of a 1-day novel desensitization protocol to olaparib. Following desensitization, the patient was successfully transitioned from olaparib capsules to tablets with no loss of tolerance. Conclusions To our knowledge, this is the first reported case of successful olaparib desensitization using a novel 1-day desensitization protocol, and will contribute to drug allergy knowledge, in an area where robust data is lacking. This case demonstrates the important role for drug desensitization in patients with immediate hypersensitivity reactions to chemotherapeutic agents. Furthermore, as olaparib capsules are being phased out in favour of olaparib tablets, we provide a clear case that transitioning from capsule to tablet form did not cause a loss of tolerance.

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Effects of Siegesbeckia pubescens on Immediate Hypersensitivity Reaction

The American Journal of Chinese Medicine ◽

10.1142/s0192415x97000184 ◽

1997 ◽

Vol 25 (02) ◽

pp. 163-167 ◽

Cited By ~ 12

Author(s):

Hyung Min Kim

Keyword(s):

Mast Cells ◽

Hypersensitivity Reaction ◽

Histamine Release ◽

Immunoglobulin E ◽

Immediate Hypersensitivity ◽

Antiallergic Activity ◽

Peritoneal Mast Cells ◽

Ige Mediated ◽

Rat Peritoneal Mast Cells ◽

Siegesbeckia Pubescens

This study was carried out to examine the effect of an aqueous extract from Siegesbeckia pubescens (Compositae) (SPAE) on immunoglobulin E (IgE)-mediated immediate hypersensitivity reaction. Forty-eight hours passive cutaneous anaphylaxis in rats was significantly inhibited by oral administration of SPAE (100 μg/g). It also inhibited histamine release from rat peritoneal mast cells induced by anti-dinitrophenyl (DNP)-IgE and DNP-human serum albumin. The data indicate that SPAE has antiallergic activity, and that its action may be due to inhibition of histamine release from mast cells.

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How to Prevent and Mitigate Hypersensitivity Reactions to Biologicals Induced by Anti-Drug Antibodies?

Frontiers in Immunology ◽

10.3389/fimmu.2021.765747 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alessandra Vultaggio ◽

Margherita Perlato ◽

Francesca Nencini ◽

Emanuele Vivarelli ◽

Enrico Maggi ◽

...

Keyword(s):

Immune Responses ◽

Cytokine Production ◽

Inflammatory Diseases ◽

Immunosuppressive Treatment ◽

Complex Structures ◽

Hypersensitivity Reactions ◽

Immediate Hypersensitivity ◽

Rheumatologic Diseases ◽

Ige Mediated ◽

Underlying Mechanisms

Biologicals are widely used therapeutic agents for rheumatologic diseases, cancers, and other chronic inflammatory diseases. They are characterized by complex structures and content of variable amounts of foreign regions, which may lead to anti-drug antibodies (ADA) development. ADA onset may limit the clinical usage of biologicals because they may decrease their safety. In fact they are mainly associated with immediate hypersensitivity reactions (HSRs). Development of ADAs is reduced by concomitant immunosuppressive treatment, while it is increased by longer intervals between drug administrations; thus, regular infusion regimens should be preferred to reduce HSRs. Once ADAs have formed, some procedures can be implemented to reduce the risk of HSRs. ADAs may belong to different isotype; the detection of IgE ADA is advisable to be assessed when high and early ADAs are detected, in order to reduce the risk of severe HRs. In patients who need to reintroduce the biological culprit, as alternative therapies are not available, drug desensitization (DD) may be applied. Desensitization should be conceptually dedicated to patients with an IgE-mediated HSR; however, it can be performed also in patients who had developed non-IgE-mediated HSRs. Although the underlying mechanisms behind successful DD has not been fully clarified, the DD procedure is associated with the inhibition of mast cell degranulation and cytokine production. Additionally, some data are emerging about the inhibition of drug-specific immune responses during DD.

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Sodium aescinate and its bioactive components induce degranulation via oxidative stress in RBL-2H3 mast cells

Toxicology Research ◽

10.1093/toxres/tfaa042 ◽

2020 ◽

Vol 9 (4) ◽

pp. 413-424

Author(s):

Xian-Ju Huang ◽

Da Gui Wang ◽

Li-Chun Ye ◽

Jun Li ◽

Muhammad Akhtar ◽

...

Keyword(s):

Oxidative Stress ◽

Mast Cells ◽

Cell Viability ◽

Intracellular Calcium ◽

Calcium Ions ◽

Great Success ◽

Hypersensitivity Reactions ◽

Immediate Hypersensitivity ◽

Stress Indices ◽

Inflammatory Conditions

Abstract Sodium aescinate (SA) is a vital salt of sodium escin from Aesculus wilsonii Rehd seeds. SA injection (SAI) has received great success in treating cerebral edema, venous reflux disease and other inflammatory conditions. Recently, high incidences of immediate hypersensitivity reactions were reported after SA infusion, which raised questions on safety and risk associated with its clinical application. This study was designed to check whether SAI and its four components induce degranulation using RBL-2H3 mast cells. For this purpose, we evaluated different treatment levels of SAI (20, 40, 60, 80 and 100 μg ml−1) and its four characteristic components, SA-A, SA-B, SA-C and SA-D, at 60 μg ml−1 in different tests including cell viability test, β-hexosaminidase and histamine assays, oxidative stress indices, apoptosis analysis and intracellular calcium ions in RBL-2H3 cells. Our results demonstrated that SAI at 80 μg ml−1 and 100 μg ml−1, and its two components (SA-B and SA-D) at 60 μg ml−1 were responsible for disturbing cell morphology and cell viability, elevated levels of β-hexosaminidase, histamine, modulation of oxidative stress indices, induced apoptosis and increase in intracellular calcium ions in RBL-2H3 cells, when compared with the control. Our results demonstrated for the first time that SAI was more likely to induce immediate hypersensitivity reactions attributable to degranulation via oxidative stress caused by SA-B and SA-D components. These results would not only be useful for the safety of end user but also for the industry to improve the quality of SA infusion.

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Hypersensitivity Reactions and Anaphylaxis

10.2310/em.4259 ◽

2020 ◽

Author(s):

Kristopher K. Ford ◽

Timothy M. Loftus ◽

Joseph J. Moellman

Keyword(s):

Mast Cells ◽

Clinical Manifestations ◽

Allergic Reactions ◽

Hypersensitivity Reactions ◽

Life Threatening ◽

Vasopressor Agents ◽

Ige Mediated ◽

Criteria For Diagnosis ◽

Key Words Allergy

Allergic reactions vary in intensity from mild rash or allergic rhinitis to devastating anaphylactic shock. Anaphylaxis, often underrecognized and undertreated, can be a life-threatening syndrome leading to multiorgan dysfunction. This review covers the etiology, pathophysiology, and treatment of severe allergic reactions and anaphylaxis. It is precipitated by exposure to particular allergens—commonly food, medications, insect stings, and environmental exposures—in a previously sensitized individual. Symptoms develop from an IgE-mediated immune response leading to degranulation of mast cells and basophils and the release of preformed mediators, lipid-derived metabolites, and inflammatory cytokines. First-line treatment for anaphylaxis involves epinephrine. Secondary treatments are antihistamines and corticosteroids. Further treatments for patients refractory to standard therapies involve vasopressor agents, nebulized albuterol, and glucagon. Frequency and duration of biphasic reactions are variable, limiting the development of consensus guidelines for monitoring of anaphylactic reactions. Figures show the immune activity and inflammatory pathways in allergic responses, mast cell degranulation, and a depiction of common organs involved and corresponding clinical manifestations. Tables list the criteria for diagnosis of anaphylaxis, classification of hypersensitivity reactions, common clinical manifestations, and etiology and mediators of anaphylaxis. This review contains 4 highly rendered figures, 11 tables, and 43 references. Key words: allergy, anaphylaxis, antihistamine, corticosteroid, epinephrine, mast cells

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