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Abstracts from the 8Th Drug Hypersensitivity Meeting (DHM)

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Abstracts from the 8Th Drug Hypersensitivity Meeting (DHM) Clin Transl Allergy 2018, 8(Suppl 3):33 https://doi.org/10.1186/s13601-018-0217-8 Clinical and Translational Allergy MEETING ABSTRACTS Open Access Abstracts from the 8th Drug Hypersensitivity Meeting (DHM) Amsterdam, the Netherlands. 19-21 April 2018 Published: 21 August 2018 THURSDAY 19 APRIL 2018 correlated with PAF concentrations, was measured by an enzymatic method. Lessons from drug induced anaphylaxis Results Anti-NMBA IgE but also anti-NMBA IgG could be detected in patients and correlated with anaphylaxis severity. Neutrophil activation mark- O01 ers as well as markers of degranulation and netosis could be meas- Evidence of an IgG‑induced neutrophil activation pathway ured in patients early after anaphylaxis onset. PAF-AH activity was during human drug‑induced anaphylaxis signifcantly lower in patients. Importantly, neutrophil activation and Luc De ­Chaisemartin1, Friederike Jönsson2, Vanessa ­Granger1, Aurélie 2 2 3 1 PAF release were associated with anaphylaxis severity and could also Gouel‑Chéron , Caitlin ­Gillis , Fadia ­Dib , Pascale Nicaise‑Roland , Chris‑ be observed in patients lacking evidence of classical IgE-dependent telle ­Ganneau4, Marie‑Thérèse ­Guinnepain5, Michel ­Aubier6, Sylvie ­Bay4, 6 7 8 anaphylaxis. Finally, anti-NMBA IgG antibodies afnity-purifed from Catherine ­Neukirch , Florence ­Tubach , Dan ­Longrois , Sylvie Chollet‑Mar‑ patient serum triggered neutrophil activation ex vivo in the presence tin1, Pierre ­Bruhns2 1 of NMBA. APHP, Hôpital Bichat, UF Auto‑immunité et Hypersensibilités, HUPNVS, Conclusion Paris, France; 2Institut Pasteur, Department of Immunology, Unit of Anti‑ 3 This study supports the existence of a pathogenic IgG-neutrophil-PAF bodies in Therapy and Pathology, Paris, France; APHP, Hôpital Bichat, pathway in human NMBA-induced anaphylaxis that may contribute to Department of Epidemiology and Clinical Research, INSERM, Paris, France; 4 anaphylaxis severity and be responsible for non-IgE mediated anaphy- Institut Pasteur, Département Biologie Structurale et Chimie, Unité de laxis in humans. Chimie des Biomolécules, Paris, France; 5Hôpital Foch, Service de méde‑ cine interne, Suresnes, France; 6APHP, Hôpital Bichat, Service de Pneu‑ mologie A, HUPNVS, Paris, France; 7INSERM, ECEVE, U1123, CIC 1421, Paris, THURSDAY 19 APRIL 2018 8 France; APHP, Hôpital Bichat, Département d’Anesthésie‑Réanimation, Beyond T cell in drug hypersensitivity HUPNVS, Paris, France Correspondence: Luc De Chaisemartin - [email protected] Clinical and Translational Allergy 2018, 8(Suppl 3):O01 O02 Oxidative stress and sulfonylarylamines hypersensitivity Background reactions: new insights Anaphylaxis is an acute systemic hypersensitivity reaction considered Abdelbaset A. Elzagallaai, Michael J. Rieder to rely on IgE antibodies against an allergen and histamine release by Western University, London, Canada mast cells and basophils. However, data from animal models suggest Correspondence: Abdelbaset A. Elzagallaai - [email protected] an alternative pathway dependent on IgG antibodies and involving Clinical and Translational Allergy 2018, 8(Suppl 3):O02 platelet-activating factor (PAF) release by monocyte/macrophages and neutrophils. Evidence of this mechanism in human is scarce and Background limited to rare allergens of high molecular weight such as dextran or Sulfonylarylamines (SAAs), such as the antibacterial sulfamethoxazole, protamine. To determine if such a pathway exists in drug anaphylaxis, are a group of very important and useful medications. However, they we conducted a multicentric study on patients with suspected ana- are associated with a major adverse reaction, namely hypersensitivity phylaxis to neuromuscular blocking agents (NMBA) during general reaction (HR), with a rate that ranges between 2% to 4% in the gen- anesthesia. eral population but can occur in nearly 50% in HIV-positive patients. Methods The pathophysiology of sulfonylarylamine-induced HRs is not well- We prospectively included 86 patients with a suspicion of NMBA- understood but accumulation of toxic reactive metabolites is thought induced anaphylaxis and 86 matched controls from 10 French anes- to be a major factor. These RMs contribute, in part, to the formation of thesia departments (NASA study). Anti-NMBA IgE and IgG levels were reactive oxygen species (ROS), which can cause cellular damage and measured by FEIA on an Immunocap 250 instrument. Expression of induce cell death through apoptosis and necroptosis. ROS can also IgE and IgG receptors on blood cells as well as activation markers on serve as ‘danger signals’ primining immune cells to mount the reaction. neutrophils were determined by fow cytometry. Circulating neutro- Methods phils extracellular traps and elastase levels were measured by ELISA. We collected blood samples from suspected SAAs HS patients (n 26), PAF-acetylhydrolase (PAF-AH) activity, a plasmatic marker inversely health volunteers (HV, n 13) and sulfonamide-tolerant patients= (ST, n 6). We then isolated= peripheral blood monocytes (PBMCs) and blood= platelets and measured the induction of cell death in these cells © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat​iveco​mmons​.org/licen​ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat​iveco​mmons​.org/ publi​cdoma​in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Clin Transl Allergy 2018, 8(Suppl 3):33 Page 2 of 74 upon in vitro challenge with diferent concentrations of the sulfameth- oxazole (SMX) reactive metabolite, sulfamethoxazole hydroxylamine (SMX-HA). We then compared the degrees of cell death with accumu- lation of ROS, lipid peroxidation, level of formation of carbonyl protein, another marker of cellular oxidative stress, and cellular glutathione contents. Results When challenged with the RM in vitro, cells isolated from SSA HS patients exhibited signifcantly (p < 0.05) higher degrees of cell death than HV and ST groups. Also ROS accumulation, lipid peroxidation and carbonyl protein levels were found to be higher in cells from patients than the HV and ST groups after challenged with RM of the drug. In addition, there was a high degree of correlation between cell death and ROS levels. Conclusion Data from this study clearly indicate a major role of oxidative stress in the pathophysiology of SAAs hypersensitivity reactions. THURSDAY 19 APRIL 2018 Skin reactions in drug allergy ‑ Poster Walk 1 P01 Cytokine profle in 133 patients with severe cutaneous adverse reactions Sophie Lalevée, Etienne Audureau, Audrey Riou, Audrey Colin, Maxime Anquetin, Caroline Barau, Laurence Valeyrie‑Allanore, Marie‑Hélène Del‑ fau‑Larue, Olivier Chosidow, Pierre Wolkenstein, Saskia Oro, Sophie Hüe Fig. 1 Results Henri Mondor Hospital, Créteil, France Correspondence: Saskia Oro - [email protected] Clinical and Translational Allergy 2018, 8(Suppl 3):P01 analysis confrmed this association between sST2 and AGEP. A high Background level of all 4 cytokines, mainly associated with EN with > 10% detached The clinical heterogenicity in Severe Cutaneous Adverse Reactions surface, was associated of a higher risk of complications. The dosage of (SCARs) (Epidermal Necrolysis, DRESS and AGEP) may be explained by IL15 will be performed to better discriminate DRESS and EN. diferent immune pathways. We studied and compared four cytokines The prognosis role of cytokine levels at diagnosis should be evaluated in the three main SCARs: TNFα and IL-6, two main cytokines of infam- with other prognostic factors such as SCORTEN. mation known to be increased in SCAR; IL1R α, antagonist receptor of IL1β involved in Th17 diferentiation; and sST2, antagonist receptor of P02 IL-33, implicated in Th2 response. Signifcant association between HLA‑B*44:03 and cold medicine Methods related Stevens–Johnson Syndrome (SJS) and Toxic Epidermal This monocenter study involved 133 patients (women 76 [57%], Necrolysis (TEN) with severe ocular complications in various mean age 48 19 years) with SCARs, 22 [16.5%] had DRESS= syndrome, ± ethnic populations 27 AGEP [20.4%], 84 [63.1%] EN including 27 Stevens–Johnson’s syn- Mayumi Ueta1, Passara Jongkhajornpong2, Tais Hitomi Wakamatsu3, Chitra dromes (SJS), 29 overlap syndromes and 28 Lyell syndromes (toxic Kannabiran4, Kaevalin Lekhanont2, José Álvaro Pereira Gomes3, Virender EN, TEN). The dosage of TNFα, IL-6, IL1Rα and sST2 was performed in Sangwan5, Chie Sotozono1, Shigeru Kinoshita1 early patients’ sera (< day 5 after admission) using Luminex technol- 1Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Ramathibodi ogy (R&D, Minneapolis, USA). A clustering analysis was made to iden- Hospital, Mahidol University, Bangkok, Thailand; 3Federal University of São tify homogenous profles of patients with similar cytokines values. Paulo, São Paulo, Brazil; 4Tej Kohli Cornea Institute, Hyderabad, India; 5L.V. We then looked for an association between those cytokine profles at Prasad Eye Institute, Hyderabad, India diagnosis and the following risk of sepsis, stay in intensive care unit Correspondence: Mayumi Ueta - [email protected] and mortality. Clinical and Translational Allergy 2018, 8(Suppl 3):P02 Results Median levels of each cytokine are reported
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