Role of T cells in nonimmediate allergic drug reactions

Rozières, Aurore; Vocanson, Marc; Saïd, B. Ben; Nosbaum, Audrey; Nicolas, Jean‐François

doi:10.1097/aci.0b013e32832d565c

Cited by 66 publications

(57 citation statements)

References 52 publications

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“…This has been confirmed by immunohistochemical studies performed in the skin, showing a mononuclear cell infiltrate composed mainly of T cells, expressing activation markers (CD25, CD69, and HLADR) and the skin-homing receptor CLA in both CD4 + and CD8 + subsets, with CD4 + cells generally predominating over CD8 + cells (Pichler 2003;Rozieres et al 2009;Torres et al 2004). Other cells such as neutrophils, eosinophils, macrophages, or keratinocytes can take part, as in MPE where increased numbers of eosinophils have been found in the papillary dermis .…”

Section: T-cell-dependent Responsesmentioning

confidence: 61%

Hypersensitivity Reactions to Beta-lactams

Torres

Mayorga

Blanca‐López

et al. 2013

T Lymphocytes as Tools in Diagnostics and Immunotoxicology

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Beta-lactam antibiotics (BLs) are the most frequent cause of hypersensitivity reactions mediated by specific immunological mechanisms, with two main types, IgE reactions or T-cell-dependent responses. From a practical point of view, these reactions can be classified into immediate, for those appearing within 1 h after drug intake, and non-immediate, for those appearing at least 1 h after and usually within 24 h of BL administration. The clinical symptoms differ according to this classification. Urticaria and anaphylaxis are the most frequently recorded symptoms in immediate reactions and maculopapular exanthema and delayed urticaria in non-immediate reactions. Although the exact diagnostic approach differs depending on the underlying mechanism, it is based on the performance of skin testing, laboratory tests, and drug provocation tests.T cells are a key factor in all types of hypersensitivity reactions to BLs, regulating both IgE production or acting as effector cells, with a different profile of cytokine production. A Th1 pattern is observed in both CD4(+) and CD8(+) peripheral T cells in non-immediate reactions, whereas a Th2 pattern is expressed in CD4(+) T cells in immediate reactions.

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Section: T-cell-dependent Responsesmentioning

confidence: 61%

Hypersensitivity Reactions to Beta-lactams

Torres

Mayorga

Blanca‐López

et al. 2013

T Lymphocytes as Tools in Diagnostics and Immunotoxicology

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“…The antigen-specific T cells proliferate, infiltrating the skin, releasing cytokines, chemokines, and proinflammatory mediators, contributing to drug rash. 4,[10][11][12][13][14] Oxaliplatin may also act as a hapten, binding to macromolecular carrier proteins, such as albumin and γ-globulin, at a rate of ≥90% 1) and acquiring immunogenicity. In this study, the Alb level in the allergy group was significantly higher than in the non-allergy group.…”

Section: Discussionmentioning

confidence: 99%

Factors Influencing the Appearance of Oxaliplatin-Induced Allergy

Nishihara

Nishikura

Morikawa

et al. 2017

Biological & Pharmaceutical Bulletin

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Several studies reported that the administration of oxaliplatin often induced allergy, but few studies have analyzed the pathogenesis. In this study, we examined the relationship between the incidence of allergy and status of oxaliplatin administration, patient background, laboratory data, or combined drugs. The subjects were 144 patients with colorectal or gastric cancer in whom oxaliplatin administration was started and completed between 2010 and 2016. They were divided into 2 groups: allergy and non-allergy groups. We extracted important factors influencing its appearance using multivariate analysis, and analyzed items of which the influence was suggested, using receiver operating characteristic (ROC) analysis. In 11 patients (7.6%), allergy appeared. The median frequency of appearance was 9 times (range: 5-13), being similar to that previously reported. On multivariate analysis, albumin (Alb) was extracted as an important factor. The cut-off value of Alb for the risk of allergy was 4.1 g/dL. An increase in the number of protein conjugates may have increased the risk of functioning as a hapten. Furthermore, the results suggested that the more frequency of oxaliplatin administration might increase the incidence of allergy, although it was not extracted as an important factor. In addition to young and female patients, as previously indicated, careful follow-up may be necessary for those with an Alb level of ≥4.1 g/dL especially after the 6th course.

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“…Immunotoxicity testing may include T-dependent antibody response (TDAR) assays, cell mediated immunity (CMI) assays, and others, depending on the drug's mode of action (Holsapple, 2003;Collinge et al, 2010Collinge et al, , 2012 and other causes for concern. Delayed-type hypersensitivity (DTH) is an important immune process and can be used to test the immunotoxic potential of drugs that target such diverse immune functions as antigen presentation, memory T-cell formation, and cytokine production (Rozieres et al, 2009). The DTH reaction to the yeast C. albicans has been historically used to test immuno-competency in humans, and therefore this infectious organism is a relevant antigen for testing immunotoxicity (Blatt et al, 1993;Yates & Deshazo, 2001).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a novel delayed-type hypersensitivity assay toCandida albicansin adult and neonatal rats

Thorn¹,

Hudson²,

Kreeger

et al. 2014

Journal of Immunotoxicology

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Delayed-type hypersensitivity (DTH) is a T-cell-mediated immune response that may be used for immunotoxicity testing in non-clinical species. However, in some cases DTH assays using T-dependent antigens may be confounded by the production of antibodies to the antigen. The authors have previously modified a DTH assay, initially validated in the mouse, for use in juvenile rats to assess the effect of immunosuppressive drugs on the developing rat immune system. The assay measures footpad swelling induced by subcutaneous footpad injection of Candida albicans (C. albicans) derived-chitosan in rats previously sensitized with C. albicans. Antibodies to chitosan are not produced in this model. However, considerable inter-animal variability inherent in the footpad swelling assay can make it difficult to precisely quantify the magnitude of the immune response and inhibition by immunosuppressants, particularly if complete suppression is not observed. This report describes the development of an ex vivo assay to assess DTH in rats using interferon (IFN)-g production by splenocytes, obtained from rats sensitized with C. albicans, as the quantifiable measure of the DTH response. Adult and neonatal rats administered dexamethasone (DEX), a known immunosuppressant, exhibited immunosuppression as evidenced by a reduction in ex vivo IFNg production from splenocytes challenged with C. albicans-derived chitosan. Current data indicate that the ex vivo based DTH assay is more sensitive than the conventional footpad swelling assay due to a lower background response and the ability to detect a response as early as post-natal day (PND) 12. The ex vivo based rat DTH assay offers a highly sensitive and quantitative alternative to the footpad swelling assay for the assessment of the immunotoxic potential of drugs. The increased sensitivity of the ex vivo DTH assay may be useful for identifying smaller changes in response to immunotoxic drugs, as well as detecting responses earlier in animal development.

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Role of T cells in nonimmediate allergic drug reactions

Cited by 66 publications

References 52 publications

Hypersensitivity Reactions to Beta-lactams

Hypersensitivity Reactions to Beta-lactams

Factors Influencing the Appearance of Oxaliplatin-Induced Allergy

Evaluation of a novel delayed-type hypersensitivity assay toCandida albicansin adult and neonatal rats

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