{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:02:29Z","timestamp":1788289349782,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Our understanding of IgE\u2010mediated drug allergy relies on the hapten concept, which is well established in\n                    <jats:italic>inducing adaptive<\/jats:italic>\n                    reactions of the immune system to small molecules like drugs. The role of hapten\u2010carrier adducts in\n                    <jats:italic>re\u2010challenge<\/jats:italic>\n                    reactions leading to mast cell degranulation and anaphylaxis is unclear. Based on clinical observations, the speed of adduct formation, skin and in vitro tests to inert drug molecules, a different explanation of IgE\u2010mediated reactions to drugs is proposed: These are (a) A natural role of reduced mast cell (MC) reactivity in developing IgE\u2010mediated reactions to drugs. This MC unresponsiveness is antigen\u2010specific and covers the serum drug concentrations, but allows reactivity to locally higher concentrations. (b) Some non\u2010covalent drug\u2010protein complexes rely on rather affine bindings and have a similar appearance as covalent hapten\u2010protein adducts. Such drug\u2010protein complexes represent so\u2010called \u201c\n                    <jats:italic>fake antigens<\/jats:italic>\n                    ,\u201d as they are unable to induce immunity, but may react with and cross\u2010link preformed drug\u2010specific IgE. As they are formed very rapidly and in high concentrations, they may cause fulminant MC degranulation and anaphylaxis. (c) The generation of covalent hapten\u2010protein adducts requires hours, either because the formation of covalent bonds requires time or because first a metabolic step for forming a reactive metabolite is required. This slow process of stable adduct formation has the advantage that it may give time to desensitize mast cells, even in already sensitized individuals. The consequences of this new interpretation of IgE\u2010mediated reactions to drugs are potentially wide\u2010reaching for IgE\u2010mediated drug allergy but also allergy in general.\n                  <\/jats:p>","DOI":"10.1111\/all.14554","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T22:51:36Z","timestamp":1597186296000},"page":"1340-1349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Anaphylaxis to drugs: Overcoming mast cell unresponsiveness by fake antigens"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8117-359X","authenticated-orcid":false,"given":"Werner J.","family":"Pichler","sequence":"first","affiliation":[{"name":"ADR\u2010AC  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13765"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2019.04.044"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-139-8-200310210-00012"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/JAA.S164806"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.08.018"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.64.4.625"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1807761"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0667-6_104"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.027797"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2020.41.190033"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e32834877c3"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14022"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000889"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3410"},{"issue":"3","key":"e_1_2_7_16_1","first-page":"403","article-title":"\u03b2\u2010lactam antibiotics epitope mapping with STD NMR spectroscopy: a study of drug\u2010human serum albumin interaction","volume":"23","author":"Milagre CDF","year":"2012","journal-title":"J Braz Chem Soc."},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.28.17940"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700209"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.183871"},{"key":"e_1_2_7_20_1","unstructured":"Vareeckal\u2010JosephS.The role of haptenation in penicillin and cephalosporin allergy doctoral thesis 2018 School of Pharmacy and Medical Sciences Division of Health Sciences Univ. of South Australia(accessable via request tohttps:\/\/find.library.unisa.edu.au)"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35113"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.anes.0000270735.40872.f2"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(02)00255-X"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.6b00253"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87492"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040810"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061316"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2010.02441.x"},{"key":"e_1_2_7_29_1","unstructured":"MuellerUR.Insect sting allergy. 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