IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells

Starkl, Philipp; Gaudenzio, Nicolas; Marichal, Thomas; Reber, Laurent L.; Sibilano, Riccardo; Watzenboeck, Martin L.; Fontaine, Frédéric; Mueller, André C.; Tsai, Mindy; Knapp, Sylvia; Galli, Stephen J.

doi:10.1111/all.14852

Cited by 20 publications

(22 citation statements)

References 38 publications

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“…A puzzling finding was the detection of neonatal fecal sIgE directed to an array of environmental allergens such as cockroach (Bla g 1, Bla g 2, Bla g 4, Bla g 5, Bla g 9, Per a 7), the tick Argas reflexus (Arg r 1), the fish parasite Anisakis simplex (Ani s 1), and insect venoms (Api m 1, Api m 10, Ves v 1, Ves v 5, Pol d 5). We speculate that such sIgE responses might relate to a broader function of immune defense of the mast cell-IgE couple, as suggested by recent findings 23,24 , harnessing the ability of maternal, and presumably fetal, sIgE to sensitize fetal mast cells 6 .…”

Section: Discussionmentioning

confidence: 62%

Multiplex Specific IgE Profiling in Neonatal Stool of Preterms Predicts IgE-mediated Disease

Sérémé¹,

Michel²,

Mezouar³

et al. 2022

Preprint

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Background: Little is known about the natural history of immunoglobulin (Ig) E-mediated diseases in preterm infants, further hampered by the lack of noninvasive investigations. We aimed at developing a non-invasive tool for the study of IgE and eosinophil-derived neurotoxin (EDN) in neonatal fecal samples and evaluating its predictive value for the development of IgE-mediated diseases (cow’s milk allergy, asthma, or atopic dermatitis) during the first year of life. Methods: We developed a stool extraction protocol, followed by freeze-drying and solubilization. sIgE responses were investigated in neonatal fecal samples from 21 preterm infants with a 300-allergen multiplex containing whole and molecular allergens and confirmed by capillary Western blot with nano-immunoassay. The local eosinophilic component was investigated by measuring the concentration of EDN. Results: The multiplexed allergen assay detected sIgE in all samples. Confirmation was obtained with Western blot. Frequency and levels of sIgE in neonatal fecal samples differed between infants who developed IgE-mediated diseases and controls. Neonatal fecal sIgE directed to milk proteins predicted later development of cow’s milk allergy (specificity 88%, sensitivity 78%). Allergen specificity of neonatal fecal sIgE was associated with later development of cow’s milk allergy and asthma. Neonatal fecal EDN levels predicted the development of IgE-mediated diseases (sensitivity 100%, specificity 75%). Conclusion: Non-invasive investigation of neonatal fecal sIgE is a promising tool for the prediction of subsequent development of IgE-mediated diseases.

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Section: Discussionmentioning

confidence: 62%

Multiplex Specific IgE Profiling in Neonatal Stool of Preterms Predicts IgE-mediated Disease

Sérémé¹,

Michel²,

Mezouar³

et al. 2022

Preprint

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“…The MC enzymes can most likely also play an important role in facilitating the influx of inflammatory cells by cleavage of connective tissue components to loosening up the compact connective tissue and also to inhibit coagulation when blood vessels open for influx of antibodies, complement and inflammatory cells. To this should be added the potent effects on numerous venoms from snakes, scorpions, Gila monster and bees ( 78 , 79 ). The effect on venoms seems to be very complex and involves all three major classes of the mast cell proteases, the chymase, the tryptase and the CPA3.…”

Section: Discussionmentioning

confidence: 99%

“…Venoms delivered by snake bites, scorpion stings or bee and wasp stings are generally appearing in the skin. Several elegant studies have shown the potent action of the different MC enzymes on these venoms resulting in their inactivation (42,(77)(78)(79)(80). The venoms also act directly on the MCs by inducing degranulation (80).…”

Section: Inactivation Of Venomsmentioning

confidence: 99%

Mast Cell and Basophil Granule Proteases - In Vivo Targets and Function

Hellman

Akula²,

Fu³

et al. 2022

Front. Immunol.

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Proteases are stored in very large amounts within abundant cytoplasmic granules of mast cells (MCs), and in lower amounts in basophils. These proteases are stored in their active form in complex with negatively charged proteoglycans, such as heparin and chondroitin sulfate, ready for rapid release upon MC and basophil activation. The absolute majority of these proteases belong to the large family of chymotrypsin related serine proteases. Three such enzymes are found in human MCs, a chymotryptic enzyme, the chymase, a tryptic enzyme, the tryptase and cathepsin G. Cathepsin G has in primates both chymase and tryptase activity. MCs also express a MC specific exopeptidase, carboxypeptidase A3 (CPA3). The targets and thereby the functions of these enzymes have for many years been the major question of the field. However, the fact that some of these enzymes have a relatively broad specificity has made it difficult to obtain reliable information about the biologically most important targets for these enzymes. Under optimal conditions they may cleave a relatively large number of potential targets. Three of these enzymes, the chymase, the tryptase and CPA3, have been shown to inactivate several venoms from snakes, scorpions, bees and Gila monster. The chymase has also been shown to cleave several connective tissue components and thereby to be an important player in connective tissue homeostasis. This enzyme can also generate angiotensin II (Ang II) by cleavage of Ang I and have thereby a role in blood pressure regulation. It also display anticoagulant activity by cleaving fibrinogen and thrombin. A regulatory function on excessive TH2 immunity has also been observed for both the chymase and the tryptase by cleavage of a highly selective set of cytokines and chemokines. The chymase also appear to have a protective role against ectoparasites such as ticks, mosquitos and leeches by the cleavage of their anticoagulant proteins. We here review the data that has accumulated concerning the potential in vivo functions of these enzymes and we discuss how this information sheds new light on the role of MCs and basophils in health and disease.

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“…Indeed, mice lacking mast cell and/or basophils were unable to acquire venom resistance after immunization 99 . Furthermore, local FcεRI‐IgE FAP mast cell degranulation enhanced venom detoxification 99,100 thanks to proteases contained in their granule such as carboxypeptidase 3 and chymase, 101,102 which degrade venom peptides (sarafotoxin and helodermin, respectively) with structure similarity to endogenous mammalian peptide (endothelin 1 and vasoactive intestinal peptide, respectively) 103 . Interestingly in those mice model of envenomation, mast cell, basophil, or even innate lymphoid cells type 2 were not required to induce IgG1 and IgE immunization against venom antigen 98,99 .…”

Section: Potential Roles Of Immunoglobulin E In Health and Non‐allerg...mentioning

confidence: 99%

Immunoglobulin E response in health and disease beyond allergic disorders

Colas

Magnan

Brouard

2022

Allergy

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Immunoglobulin E is the latest discovered of immunoglobulin family and has been long associated with anaphylaxis and worm expulsion. Immunoglobulin E, along with mast cells, basophils, and eosinophils, is also a hallmark of type 2 immunity which is dysregulated in numerous diseases such as asthma, rhinitis, atopic dermatitis, and eosinophilic esophagitis in addition to anaphylaxis as aforementioned. However, recent advances have shed light on IgE regulation and memory explaining the low level of free IgE, the scarcity of IgE plasma cells that are mainly short live and the absence of IgE memory B cells in homeostatic conditions. Furthermore, IgE was implicated in inflammatory conditions beyond allergic disorders where IgE‐mediated facilitated antigen presentation can enhance cellular and humoral response against autoantigens in systemic lupus or chronic urticaria leading to more severe disease and even against neoantigen facilitating tumor cell lysis. At last, IgE was unexpectedly associated with allograft rejection or atheromatous cardiovascular diseases where precise mechanisms remain to be deciphered. The purpose of this review is to summarize these recent advances in IgE regulation, biology, and physiopathology beyond allergic diseases opening whole new fields of IgE biology to explore.

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IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells

Cited by 20 publications

References 38 publications

Multiplex Specific IgE Profiling in Neonatal Stool of Preterms Predicts IgE-mediated Disease

Multiplex Specific IgE Profiling in Neonatal Stool of Preterms Predicts IgE-mediated Disease

Mast Cell and Basophil Granule Proteases - In Vivo Targets and Function

Immunoglobulin E response in health and disease beyond allergic disorders

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