{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:49:50Z","timestamp":1792633790161,"version":"4.5.0"},"reference-count":144,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>MRGPRX2, a novel G<jats:sub>aq<\/jats:sub>\u2010coupled human mast cell receptor, mediates non\u2010immune adverse reactions without the involvement of antibody priming. Constitutively expressed by human skin mast cells, MRGPRX2 modulates cell degranulation producing pseudoallergies manifesting as itch, inflammation and pain. The term pseudoallergy is defined in relation to adverse drug reactions in general and immune\/non\u2010immune\u2010mediated reactions in particular. A list of drugs with MRGPRX2 activity is presented, including a detailed examination of three important and widely used approved therapies: neuromuscular blockers, quinolones and opioids. For the clinician, the significance of MRGPRX2 is considered as an aid in distinguishing and ultimately identifying specific immune and non\u2010immune inflammatory reactions. Anaphylactoid\/anaphylactic reactions, neurogenic inflammation and inflammatory diseases with a clear or strongly suspected association with MRGPRX2 activation are examined. Inflammatory diseases include chronic urticaria, rosacea, atopic dermatitis, allergic contact dermatitis, mastocytosis, allergic asthma, ulcerative colitis and rheumatoid arthritis. MRGPRX2\u2010 and allergic IgE\/Fc\u03b5RI\u2010mediated reactions may be clinically similar. Importantly, the usual testing procedures do not distinguish the two mechanisms. Currently, identification of MRGPRX2 activation and diagnosis of pseudoallergic reactions is generally viewed as a process of exclusion once other non\u2010immune and immune processes, particularly IgE\/Fc\u03b5RI\u2010mediated degranulation of mast cells, are ruled out. This does not take into account that MRGPRX2 signals via \u03b2\u2010arrestin, which can be utilized to detect MRGPRX2 activation by employing <jats:italic>MRGPRX2<\/jats:italic> transfected cells to assess MRGPRX2 activation via two pathways, the G\u2010protein\u2010independent \u03b2\u2010arrestin pathway and the G\u2010protein\u2010dependent Ca<jats:sup>2+<\/jats:sup> pathway. Testing procedures, interpretations for distinguishing mechanisms, patient diagnosis, agonist identification and drug safety evaluations are addressed.<\/jats:p>","DOI":"10.1111\/bcp.15845","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T04:04:47Z","timestamp":1689048287000},"page":"3232-3246","source":"Crossref","is-referenced-by-count":44,"title":["MRGPRX2, drug pseudoallergies, inflammatory diseases, mechanisms and distinguishing MRGPRX2\u2010 and IgE\/Fc\u03b5RI\u2010mediated events"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-4865","authenticated-orcid":false,"given":"Brian A.","family":"Baldo","sequence":"first","affiliation":[{"name":"Royal North Shore Hospital of Sydney Kolling Institute of Medical Research  Sydney New South Wales Australia"},{"name":"Department of Medicine University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010030\u201051740\u20103"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14022"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.08.177"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.676354"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2011.08.015"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051033"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204\u2010022\u201003402\u20102"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85538"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00299"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.06.030"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2022.12.014"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15270"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01283a038"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00269a016"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/57.6.550"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/58.8.834"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010198903000\u201000003"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/77.3.421"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495\u2010199753050\u201000012"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2018.04.014"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13456"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0161\u20105890(83)90171\u20102"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102222.2008.03171.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/0310057X0002800207"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31820164d2"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20106576.2011.02598.x"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/55.2.113"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010199702000\u201000008"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/76.5.624"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.07.020"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2018.08.005"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.668962"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12099"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.2310\/6620.2011.10115"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmacy7030097"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.09.035"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398\u20109995.2010.02460.x"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2014.12.012"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13236"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014\u20102999(00)00147\u20103"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1211\/0022357001774228"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010198910000\u201000003"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/0310057X1204000204"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204\u2010021\u201003068\u20102"},{"key":"e_1_2_11_46_1","first-page":"305","article-title":"Endermic reactions","volume":"9","author":"Sollmann T","year":"1917","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010199211000\u201000016"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2334"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003643\u2010200106000\u201000002"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(88)90085\u20101"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970\u20109185.117045"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006123\u2010199111000\u201000025"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002730"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.09.017"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.01.059"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.09.038"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12622"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102222.1995.tb01013.x"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.05.004"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2014.4728"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.04.051"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.01.012"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.1967.tb01984.x"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/72247"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.139.11.1479"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.11.013"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12266"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00422"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102222.2009.03256.x"},{"issue":"11","key":"e_1_2_11_70_1","first-page":"717","article-title":"Acute and chronic urticaria: evaluation and treatment","volume":"95","author":"Schaefer P","year":"2017","journal-title":"Am Fam Physician"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140\u20106736(92)91000\u2010x"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1398\u20109995.1999.00726.x"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12948\u2010018\u20100101\u2010z"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091\u20106749(86)90260\u20105"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.04.043"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1080\/19381980.2017.1361574"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16481"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102133.2012.11037.x"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2004.01.048"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1616"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403\u2010007\u20100816\u2010z"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.222"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13143"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281\u2010018\u20100675\u2010z"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.01.053"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.06.016"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.3389\/falgy.2021.702488"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010023\u201000992\u20104"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010019\u20100493\u2010z"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.O\u201007\u2010486"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20101568\u20102_30"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.12.029"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2000.105528"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1097\/itx.0000000000000005"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882\u2010020\u201000979\u20105"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.028"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2016.08.014"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2019.08.012"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.03.088"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.013"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2019.07.007"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.13292"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.08.034"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.05.042"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2022.10.053"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2022.10.054"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.930945"},{"key":"e_1_2_11_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2014.09.004"},{"key":"e_1_2_11_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.11.008"},{"key":"e_1_2_11_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.01.022"},{"key":"e_1_2_11_111_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00821"},{"key":"e_1_2_11_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.01.012"},{"key":"e_1_2_11_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.01.056"},{"key":"e_1_2_11_114_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010017\u20100698\u20103"},{"key":"e_1_2_11_115_1","doi-asserted-by":"publisher","DOI":"10.1038\/80826"},{"key":"e_1_2_11_116_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465\u20109921\u201011\u2010139"},{"key":"e_1_2_11_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.07.036"},{"key":"e_1_2_11_118_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102222.1995.tb01024.x"},{"key":"e_1_2_11_119_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.151.3.7533601"},{"key":"e_1_2_11_120_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.150"},{"key":"e_1_2_11_121_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.20805.1"},{"key":"e_1_2_11_122_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005758108"},{"key":"e_1_2_11_123_1","doi-asserted-by":"publisher","DOI":"10.2478\/v10039\u2010012\u20100029\u20103"},{"key":"e_1_2_11_124_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.121"},{"key":"e_1_2_11_125_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.076"},{"key":"e_1_2_11_126_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003840050136"},{"key":"e_1_2_11_127_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13579"},{"key":"e_1_2_11_128_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.04.001"},{"key":"e_1_2_11_129_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.1991.tb33147.x"},{"key":"e_1_2_11_130_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem301"},{"key":"e_1_2_11_131_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2017.03.002"},{"key":"e_1_2_11_132_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2022.11.001"},{"key":"e_1_2_11_133_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109237"},{"key":"e_1_2_11_134_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710487105"},{"key":"e_1_2_11_135_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3014"},{"key":"e_1_2_11_136_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057108321531"},{"key":"e_1_2_11_137_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057113475480"},{"key":"e_1_2_11_138_1","doi-asserted-by":"publisher","DOI":"10.1080\/1547691X.2020.1757793"},{"key":"e_1_2_11_139_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801227"},{"key":"e_1_2_11_140_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.03.049"},{"key":"e_1_2_11_141_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.12.805"},{"key":"e_1_2_11_142_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10112906"},{"key":"e_1_2_11_143_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/160.5.876"},{"key":"e_1_2_11_144_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246\u2010199909000\u201000006"},{"key":"e_1_2_11_145_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14747"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15845","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T06:43:09Z","timestamp":1697697789000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.15845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":144,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/bcp.15845"],"URL":"https:\/\/doi.org\/10.1111\/bcp.15845","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,8]]}}}