In vitro Diagnosis of Immediate Drug Hypersensitivity: Should We Go with the Flow?

Mangodt, Evelyne; Gasse, Athina L. Van; Decuyper, Ine I.; Uyttebroek, Astrid P.; Faber, Margaretha A.; Sabato, Vito; Bridts, Chris H.; Hagendorens, Margo M.; Ebo, Didier G.

doi:10.1159/000440663

Cited by 36 publications

(16 citation statements)

References 61 publications

(73 reference statements)

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“…Drug allergy was suspected in children who had a history of any reaction after a specific drug intake; it was confirmed by measuring drug-specific IgE and/or SPT and/or a drug provocation test [8]. The diagnosis of FA in children with a history of symptoms associated with specific food intake and/or those with food sIgE ≥0.35 kU/l and/or a positive SPT was made after an elimination diet with a food challenge.…”

Section: Methodsmentioning

confidence: 99%

The ADAPAR Birth Cohort Study: Food Allergy Results at Five Years and New Insights

Doğruel

Bingöl

Yılmaz

et al. 2016

Int Arch Allergy Immunol

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Background: Although food allergy (FA) is often a transient condition during childhood, when and in whom FA will resolve can be affected by many factors. In this study, we analyzed the data at 5 years on 33 children diagnosed with FA in the ADAPAR (Adana Pediatric Allergy Research) birth cohort study in southern Turkey. Methods: Thirty-three infants detected as having FA at the end of their first year in the ADAPAR study were assessed every 6 months until the age of 5 years. Each follow-up included a clinical examination, questionnaire, blood sampling and a skin-prick test. Results: Culprit allergens were cow's milk (n = 20), eggs (n = 17), chicken meat (n = 1) and bananas (n = 1). Of the 17 patients with egg allergy, 14 developed complete tolerance and 1 developed partial tolerance (i.e. tolerance to baked food). Of the 20 patients with milk allergy, complete tolerance was observed in 16 and partial tolerance in 1. The mean age of tolerance to egg was 22.4 ± 7.5 months and to cow's milk, it was 20.9 ± 1.1 months. Complete tolerance developed in 1 case allergic to chicken meat and in 1 case allergic to banana. Other allergic conditions were also determined: allergic rhinitis in 27.2%, atopic dermatitis in 21.2%, asthma in 9%, urticaria in 9% and drugs in 9%. Conclusions: Our results confirm early and high tolerance rates before school age in children with food allergies that started in infancy. This will help pediatricians to give more informed advice to parents of infants with cow's milk or hen's egg allergy.

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Section: Methodsmentioning

confidence: 99%

The ADAPAR Birth Cohort Study: Food Allergy Results at Five Years and New Insights

Doğruel

Bingöl

Yılmaz

et al. 2016

Int Arch Allergy Immunol

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“…The test tubes are then rotated at 4°C and 200´g for 5 min. After the tubes are prepared, in order to select the basophil and measure the activity before starting to work in flow cytometry, the cells are stained with 20 μL monoclonal anti-human IgE, 10 μL monoclonal CD63, and 10 μL CD203C antibodies on ice for 20 min (9)(10)(11)(12)(13)(14). Then, the tubes are worked on in the flow cytometry.…”

Section: Basophil Activation Test: How Is the Activation Of In Vitro mentioning

confidence: 99%

“…Sometimes, they are used together in the evaluations. It is known that the sensitivity and specificity of BAT increase when they are used together (9)(10)(11)(12)(13)(14).…”

Section: Basophil Activation Test: How Is the Activation Of In Vitro mentioning

confidence: 99%

“…In the review presented by Mangodt et al (11,12) in 2015, BAT was seen as a useful diagnostic tool in the allergies developing against NMBA, antibiotics, NSAIDs, and iodinated RCA. In drug allergies other than quinolones and NSAIDs, it was reported that the sensitivity reached 50% to 60% and the specificity reached 80% in general.…”

Section: The Review On the Use Of Bat In Early Dhrmentioning

confidence: 99%

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Basophil Activation in Immediate Drug Hypersensitivity Reactions and Basophil Activation Test (BAT)

Özdemir¹

2017

Istanbul Med J

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New pathways and hypotheses continue to be described in the etiopathogenesis of early drug hypersensitivity reactions (DHR) to antibiotics such as penicillin and drugs such as aspirin and nonsteroidal anti-inflammatory drug (NSAID). The best-known hypotheses are the hapten/prohapten and pharmacological interactions (p-i) concept (1).Hapten/Pro-hapten concept: Small-molecular-weight drugs (hapten) and the reagent intermediates/metabolites (pro-hapten) formed after the metabolism of the drug cannot cross-link with Fcε-RI by themselves (2). In reference to the concept of hapten and pro-hapten, it is thought that basophils play a role in early developing DHRs. P-i concept:T lymphocytes develop delayed-type immune reactions in the result of the interaction of the drugs (lidocaine, sulfamethoxazole, lamotrigine, etc.) with T cells via immunoreceptors, and basophils do not have any role here (3).As these three hypotheses reveal, it is understood that basophils and their activation play a role in the development of early DHR. The diagnosis of early DHR is usually dependent upon the history, prick, or intradermal skin tests and the determination of the amount of specific immunoglobulin E (IgE) antibodies that develop against the drug (4). These methods are often insufficient in IgEmediated reactions and useless in non-IgE-mediated reactions. Although drug provocation tests are accepted as the gold standard, they cannot always be performed because of ethical and practical reasons (5). Therefore, there is a need for the development of in vitro tests such as basophil activation test (BAT), which is based on the examination of cells (basophil and mast cell) involved in such allergic reactions (6).Basophil activation test is a test showing IgE-mediated and non-IgE-mediated mast and basophil cell degranulation. Stimulation with stimulant drug or metabolite is based on the identification of basophils by flow cytometry (anti-IgE, CCR3, CRTH2, and CD203c expression, etc.) and on their activation level (through the expressions of CD63 and CD203c) (7). Basophil Activation in Immediate Drug Hypersensitivity Reactions and Basophil Activation Test (BAT)In the basophil activation test (BAT), the expression of the degranulation marker lysosomal-associated membrane glycoprotein-3, also termed as CD63, or upregulation of CD203c is determined. Degranulation is the fusion of specific intracellular vesicles filled with preformed mediators, which are the so-called granules, with the plasma membrane and the transition of CD63 from inside out. The result is a sudden and pronounced rise, i.e., log shift, of the fluorescence intensity signal in the detection of surface CD63 molecule. Concomitantly, the upregulation of CD203c has been observed; this can be detected as a significant increase in the mean fluorescence intensity signal of the CD203c detection antibody. The most common identification strategies use surface IgE, eotaxin CC chemokine receptor 3, the interleukin-3 receptor alpha chain CD123, the prostaglandin D2 receptor CRTH-2, or the ba...

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“…However, in patients who experienced IHR, extensive skin allergic investigations (Prick tests and intradermal tests [IDT]) were often negative [13]. Functional tests exploring the in vitro activation of basophils induced by IFX and mimicking cell immunologic events that lead to the onset of clinical symptoms in vivo have been more recently developed [23]. Basophil activation tests (BAT) are now increasingly widespread and used for the diagnosis of specific allergy to drugs [24], but the usefulness of such in vitro tests in IHR to IFX is unknown.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Infliximab Tolerance Induction in Patients with Inflammatory Bowel Diseases who Experienced Acute Infusion Reactions

Pauchard

Nancey

Hacard

et al. 2018

Dig Dis

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Background and Aims: One of the reasons for the failure of infliximab (IFX) is immediate hypersensitivity reactions (IHR). We aimed to report the efficacy and safety of a tolerance induction protocol in inflammatory bowel diseases (IBD) patients who had previously experienced IHR during IFX infusions. Patients and Methods: We reported all cases of IBD patients who had previously experienced IHR due to IFX and who were submitted to a standardized protocol of tolerance induction to IFX from 2010 to 2015. Results: IHR occurred in a majority of patients (69%) during the first 3 infusions and for half of them after a period of IFX withdrawn. Skin prick tests were negative and only 2 intradermal tests were positive. Basophil activation tests and antidrug antibody measurements were performed in 8 out of 16 patients and were positive in 3 and 4 patients respectively. Induction of tolerance was successful in 69% of patients and IFX was pursued with clinical efficacy > 1 year in 7 patients (44%). Allergologic investigations were not predictive of tolerance induction success. Conclusion: A majority of IHR to IFX infusions occurred during the beginning or restarting of treatment and was related to a nonallergic hypersensitivity. Induction of tolerance to IFX is feasible and effective and may safely allow retreatment of IFX in almost 70% of IBD patients.

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In vitro Diagnosis of Immediate Drug Hypersensitivity: Should We Go with the Flow?

Cited by 36 publications

References 61 publications

The ADAPAR Birth Cohort Study: Food Allergy Results at Five Years and New Insights

The ADAPAR Birth Cohort Study: Food Allergy Results at Five Years and New Insights

Basophil Activation in Immediate Drug Hypersensitivity Reactions and Basophil Activation Test (BAT)

Efficacy and Safety of Infliximab Tolerance Induction in Patients with Inflammatory Bowel Diseases who Experienced Acute Infusion Reactions

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