Associations between HLA-A, -B, and -C alleles and iodinated contrast media– induced hypersensitivity in Koreans

김은영,최석진,Jong-Lyul Ghim,김미영,설정은,Minkyung Oh,Chan Sun Park,신재국 대한임상약리학회 2021 Translational and Clinical Pharmacology Vol.29 No.2

A common cause of drug hypersensitivity reactions is iodinated contrast media (ICM). ICM-induced hypersensitivity had been considered to be a non-immunological reaction,but evidence for an immunological mechanism has increased recently. Thus, we evaluatedwhether HLA-A, -B, and -C alleles were associated with ICM-induced hypersensitivity. Intotal, 126 patients who underwent contrast-enhanced computed tomography studies throughoutpatient clinics at a tertiary referral hospital between 2008 and 2012 were assessed. Sixty-one patients experienced ICM-induced hypersensitivity and the remainder, 65, wereICM-tolerant patients (control). ICM-induced hypersensitivity patients showed 51 withimmediate, 7 with non-immediate, 3 with both or mixed type. HLA-A, -B, and -C genotypingwas performed using a PCR sequence-based typing method. Four kinds of ICM were used:iopromide, iohexol, iobitridol, and iodixanol. The most used ICM among the hypersensitivitypatients was iopromide. Significant difference in the frequency of HLA-B*58:01 (odds ratios[OR], 3.90; p = 0.0200, 95% confidence interval [CI], 1.16–13.07) was observed betweenICM-induced immediate hypersensitivity and control. There were statistically significantdifferences in the frequencies of the HLA-B*38:02 (OR, 10.24; p = 0.0145; 95% CI, 1.09–96.14)and HLA-B*58:01 (OR, 3.98; p = 0.0348; 95% CI, 1.03–15.39) between iopromide-inducedimmediate hypersensitivity and control. The mechanism of ICM-induced hypersensitivityremains unknown, but this study showed associations, although weak, with HLA-B*58:01 allelesfor ICM-induced immediate hypersensitivity and HLA-B*38:02 and HLA-B*58:01 for iopromideinducedimmediate hypersensitivity as risk predictors. Further studies are needed to validate theassociations in larger samples and to identify the functional mechanism behind these results.

Immediate Hypersensitivity to Quinolone

( Young Hee Nam ),( Jeong Eun Kim ),( Seung Hyun Kim ),( Hyun Jung Jin ),( Eui Kyung Hwang ),( Young Min Ye ),( Yoo Seob Shin ),( Hae Sim Park ) 대한내과학회 2011 대한내과학회 추계학술발표논문집 Vol.2011 No.1

Background/Aims: Quinolone hypersensitivity is rare, but most reactions are immediate onset characterized by the presence of urticaria, angioedema and anaphylaxis. The pathogenic mechanisms underlying immediate reactions are not defined clearly. We investigated the pathogenic mechanisms with detection of serum specific IgE to quinolone. Methods: We recruited 12 patients presenting immediate hypersensitivity reactions to olfoxacin and/or ciprofloxacin from Ajou University Hospital. Allergy skin test and oral challenge test were performed. Serum specific IgE antibody to ofloxacin-human serum albumin (HSA) conjugate was detected by ELISA, and ELISA inhibition tests were performed with additions of olfloxacin-HSA conjugate, free forms of ofloxain, ciprofloxacin and levofloxacin. Results: Eleven were females (91.7%) with a mean age of 39.6 years. The culprit drugs were ofloxacin in 5 patients (group I) and ciprofloxacin in 7 patients (group 2). Major symptoms were urticaria/angioedema in 7 patients and anaphylaxis in 5 patients. Serum specific IgE to ofloxacin-HSA conjugate was detected in 4(80%) of group 1, and 3(50%) of group 2 patients. Significant inhibitions were noted with additions of olfloxacin-HSA conjugate, free forms of olfloxacin, ciprofloxacin and levofloxacin which showed different patterns individually. Conclusions: We confirmed that IgE mediate response is a major pathogenic mechanism of quinolone hypersensitivity. Cross reactivity among the three quinolones were noted with individual difference.

Clinical Features of Immediate Hypersensitivity to Isopropylantipyrine

황의경,남영희,진현정,신유섭,예영민,박해심 대한천식알레르기학회 2013 Allergy, Asthma & Immunology Research Vol.5 No.1

Hypersensitivities induced by isopropylantipyrine (IPA), a pyrazolone derivative within the wider family of non-steroidal anti-inflammatory drugs(NSAIDs), are rarely reported. We characterized the clinical features of 12 patients with IPA-induced hypersensitivity. Twelve patients with immediatehypersensitivity to IPA were enrolled and classified into two groups: group I, consisting of eight patients (66.7%) with selective hypersensitivity;and group II, consisting of four patients (33.3%) showing cross-intolerance to other NSAIDs. Skin prick and intradermal and oral provocation testswith IPA were performed. To confirm selective hypersensitivity, an aspirin oral provocation test was also conducted. The most common manifestationswere cutaneous reactions (91.7%), followed by anaphylaxis (66.7%), respiratory (41.7%), ocular (16.7%), and gastrointestinal reactions (16.7%). The median age and the median age at onset were 34.5 (range, 23-55) years and 28.0 (range, 7-47) years, respectively. In both groups I and II, all patientsshowed negative responses to skin prick testing, whereas only two patients in group I were positive in response to intradermal IPA tests. Theresponse time after drug exposure was shorter in group I than in group II. Here, we report on two types of IPA hypersensitivity: selective and crossintolerantNSAID hypersensitivity. An immediate IgE-mediated reaction may be involved in patients with selective hypersensitivity, whereas a cyclooxygenase-1-related inhibition mechanism may be a responsible mechanism for the patients with cross-intolerance to multiple NSAIDs.

Immunologic Evaluation of Ofloxacin Hypersensitivity

Nam, Young-Hee,Kim, Jeong Eun,Kim, Seung-Hyun,Jin, Hyun Jung,Hwang, Eui-Kyung,Shin, Yoo Seob,Ye, Young-Min,Park, Hae-Sim The Korean Academy of Asthma, Allergy and Clinical 2012 Allergy, Asthma & Immunology Research Vol.4 No.6

<P>Quinolone hypersensitivity, most of which is immediate type, is rare but has increased in recent years. The pathogenic mechanisms underlying immediate reactions are not defined clearly. This study was aimed to observe the clinical characteristics of immediate hypersensitivity to ofloxacin and to investigate the pathogenic mechanism with detection of serum specific IgE to ofloxacin using an enzyme-linked immunoasorbent assay (ELISA). We recruited 5 patients with immediate hypersensitivity reactions to ofloxacin (group I), and as control groups, 5 subjects with ciprofloxacin hypersensitivity (group II) and 20 healthy subjects with no history of drug allergy. Serum specific-IgE to ofloxacin-human serum albumin (HSA) conjugate was detectable in four group I subjects (80%) and three group II subjects (60%). The ELISA inhibition test showed significant inhibition with both ofloxacin-HSA conjugate and free ofloxacin in a dose-dependent manner. As to ciprofloxacin, significant inhibition was noted upon addition of free ciprofloxacin in one subject, while minimal inhibition was noted in the other. We confirmed that an IgE-mediated response is a major pathogenic mechanism of ofloxacin hypersensitivity. Cross reactivity between ofloxacin and ciprofloxacin was noted with individual difference.</P>

Cefaclor 즉시형 과민반응을 나타낸 환자들의 임상적 및 면역학적 특징

남영희 ( Young Hee Nam ),김정은 ( Jeong Eun Kim ),황의경 ( Eui Kyung Hwang ),진현정 ( Hyun Jung Jin ),신유섭 ( Yoo Seob Shin ),예영민 ( Young Min Ye ),남동호 ( Dong Ho Nahm ),박해심 ( Hae Sim Park ) 대한천식알레르기학회 2011 천식 및 알레르기 Vol.31 No.3

Background: Cefaclor is commonly prescribed for various infectious diseases. It is known as a major causative antibiotic that induces drug hypersensitivity reactions. The aim of this study is to evaluate clinical and immunologic features of cefaclor immediate hypersensitivity. Methods: We conducted a retrospective study on the patients with histories of immediate hypersensitivity to cefaclor at Ajou University Hospital between January 2002 and February 2011. Serum specific IgE to cefaclor was measured using the ImmunoCAP system. Results: Fifty patients were enrolled in this study. The most common immediate hypersensitivity reaction was anaphylaxis (38/50, 76%), followed by urticaria/angioedema (12/50, 24%). High serum specific IgE to cefaclor was noted in 40 patients (80%). There were no significant differences in clinical parameters whether the patients had serum specific IgE or not, except that serum total IgE level was higher in patients with high serum specific IgE to cefaclor (P=0.042). Serum specific IgE to penicillin was detected in 26.1% of the patients with high serum specific IgE to cefaclor, while serum specific IgE to aminopenicillin was not found in any of the study subjects. Conclusion: Immediate hypersensitivity to cefaclor occurred mostly through the IgE-mediated mechanism, and anaphylaxis was the most common manifestation. Cross reactivity with penicillin was noted in 26% of the patients, but no cross reactivity with aminopenicillin was noted. (Korean J Asthma Allergy Clin Immunol 2011;31:192-198)

Immunologic Evaluation of Ofloxacin Hypersensitivity

남영희,김정은,김승현,진현정,황의경,신유섭,예영민,박해심 대한천식알레르기학회 2012 Allergy, Asthma & Immunology Research Vol.4 No.6

Quinolone hypersensitivity, most of which is immediate type, is rare but has increased in recent years. The pathogenic mechanisms underlying immediate reactions are not defined clearly. This study was aimed to observe the clinical characteristics of immediate hypersensitivity to ofloxacin and to investigate the pathogenic mechanism with detection of serum specific IgE to ofloxacin using an enzyme-linked immunoasorbent assay (ELISA). We recruited 5 patients with immediate hypersensitivity reactions to ofloxacin (group I), and as control groups, 5 subjects with ciprofloxacin hypersensitivity (group II) and 20 healthy subjects with no history of drug allergy. Serum specific-IgE to ofloxacin-human serum albumin (HSA) conjugate was detectable in four group I subjects (80%) and three group II subjects (60%). The ELISA inhibition test showed significant inhibition with both ofloxacin-HSA conjugate and free ofloxacin in a dose-dependent manner. As to ciprofloxacin, significant inhibition was noted upon addition of free ciprofloxacin in one subject, while minimal inhibition was noted in the other. We confirmed that an IgE-mediated response is a major pathogenic mechanism of ofloxacin hypersensitivity. Cross reactivity between ofloxacin and ciprofloxacin was noted with individual difference. Keywords: Cross reactivity, enzyme-linked immunosorbent assay, IgE, immediate hypersensitivity, ofloxacin.

Prevalence of Immediate-Type Food Allergy in Early Childhood in Seoul

박미란,김지현,김도수,안강모,한영신 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.2

Purpose: There are scanty epidemiologic data on the prevalence of food allergy (FA) among preschool children in Asia. We performed this study todetermine the prevalence and causative foods of immediate-type FA in early childhood in Korea. Methods: A questionnaire-based, cross-sectionalstudy was performed between September and October 2011. Children aged 0-6 years were recruited from 301 public child care centers in Seoul. Parents were asked to complete a questionnaire on FA. Children with FA were classified into “perceived FA, ever,” “immediate-type FA, ever,” and“immediate-type FA, current” according to the algorithm. Results: A total of 16,749 children were included in this study. The prevalence of “perceivedFA, ever,” “immediate-type FA, ever,” and “immediate-type FA, current” was 15.1%, 7.0%, and 3.7%, respectively. “Immediate-type FA, current”was reported by 182 (4.9%) out of 3,738 children aged ≤2 years, 262 (3.4%) of 7,648 children aged 3-4 years, and 177 (3.3%) of 5,363 childrenaged 5-6 years. Hen’s egg (126/621) was the most frequent cause as the individual food item, followed by cow’s milk (82/621) and peanut (58/621). Among the food groups, fruits (114/621), tree nuts (90/621) and crustaceans (85/621) were the most common offending foods. The three leadingcauses of food-induced anaphylaxis were hen’s egg (22/47), cow’s milk (15/47), and peanut (14/47). Conclusions: The prevalence of immediatetypeFA in early childhood is 3.7%, and is higher in younger children. The most common offending foods differed with age.

Effect of <i>Dracocephalum argunense</i> on Mast-Cell-Mediated Hypersensitivity

Kim, Sang-Hyun,Shin, Tae-Yong S. Karger AG 2006 International archives of allergy and immunology Vol.139 No.2

<P><I>Background:</I> Stimulation of mast cells starts the process of degranulation resulting in release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of an aqueous extract of <I>Dracocephalum argunense</I> Fisch. (Labiatae) (DAAE) on immediate-type hypersensitivity and studied its possible mechanisms of action, focusing on histamine release and proinflammatory cytokine expression in mast cells. <I>Methods:</I> An in vivo model of systemic and local allergic reaction was investigated. Compound 48/80- or IgE-induced histamine release from mast cells was measured. The expression of proinflammatory cytokines such as TNF-α and IL-6 was measured by RT-PCR and ELISA. The level of intracellular calcium was measured by spectrofluorometry. NF-κB activation was measured by Western blot, EMSA and luciferase assay. <I>Results:</I> DAAE inhibited systemic anaphylaxis, local allergic reactions, and serum histamine release in a dose-dependent manner in mice. DAAE dose-dependently reduced histamine release from mast cells activated by compound 48/80 or IgE. The inhibitory effect of DAAE on histamine release was mediated by the modulation of intracellular calcium. In addition, DAAE decreased TNF-α and IL-6 gene expression and production in human mast cells stimulated by phorbol-12-myristate-13-acetate (PMA) plus calcium ionophore A23187. The inhibitory effect of DAAE on the TNF-α and IL-6 expression was NF-κB dependent. <I>Conclusion:</I> Our findings provide evidence that DAAE inhibits mast-cell-derived immediate-type hypersensitivity. Taken together, the anti-allergic effect of DAAE in vivo and in vitro suggests a possible clinical use of this agent in immediate-type hypersensitivity.</P><P>Copyright © 2006 S. Karger AG, Basel</P>

가미옥액탕이 즉시형 과민반응에 미치는 영향

총배빈,강경화,김원일,Tsung, Pei-Yun,Kang, Kyung-Hwa,Kim, Won-Il 대한한방안이비인후피부과학회 2006 한방안이비인후피부과학회지 Vol.19 No.3

Object : We investigated the effect of Gamiokyaek-tang (GOYT) on immediate type hypersensitivity. Methods : We investigated anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis and acetic acid-induced vascular permeability in rodents. Also perfonned MTT assay and b-hexosaminidase activity is measured in RBL-2H3. Results : GOYT inhibited passive cutaneous anaphylaxis and acetic acid-induced vascular permeability by oral administration. All the concentrations of GOYT from 0.1 to 5 mg/ml didn't have an effect on cell viability and cytotoxicity. b-hexosaminidase release in RBL-2H3 was significantly reduced by 2 and 5 mg/ml of GOYT. Conclusion : These results indicate that GOYT have inhibition effects on immediate type hypersensitivity .

구보음(九寶飮)과 가미구보음(加味九寶飮)이 폐혈전색전(肺血栓塞栓) 및 즉시형(卽時型) Allergy반응(反應)에 미치는 영향(影響)

김경민,강병령,박동일,정광식,Kim, Gyoung-Min,Gang, Byoung-Ryoung,Park, Dong-Il,Jeong, Gwang-Sik 대한한방내과학회 2000 大韓韓方內科學會誌 Vol.21 No.4

Objective : Experimental studies were done to research the effects of Gubo-eum(Jiubao-yin) and Kamigubo-eum(Jiameijiubao-yin) on the pulmonary thromboembolism and the immediately type hypersensitivity. Methods : For measuring the response about the pulmonary thromboembolism, we investigated a survival rate after the intravenous injection of sodium arachidonate and adenocine diphophate(ADP). For measuring the response about the immediately type hypersensitivity, we did the intravenous injection of histamin and serotonin, and phlebotomized and excoriated skin and investigated the amount of escaped pigment. Results : The each solid extract of Gubo-eum(Jiubao-yin) and Kamigubo-eum(Jiameijiubao-yin) revealed significant decrease effect on viscosity of mucin solution. The each solid extract of Gubo-eum(Jiubao-yin) and Kamigubo-eum(Jiameijiubao-yin) revealed significant effect on the pulmonary thromboembolism induced by sodium arachidonate and adenocine diphophate(ADP). The each solid extract of Guboeum(Jiubao-yin) and Kamigubo-eum(Jiameijiubao-yin) revealed significant on vascular permeability responses to intradenmal histamine and serotonine. conclusions : The each solid extract of Gubo-eum(Jiubao-yin) and Kamigubo-eum(Jiameijiubao-yin) revealed significant effect on the immediately type hypersensitivity and the pulmonary thromboembolism.