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T cell-and non T cell-mediated delayed hypersensitivity to dupilumab We hypothesize that Patient 1 was sensitized to T-cell epitopes in the tralokinumab primary sequence with cross-reactivity with dupilumab[6]; (ii) an Arthus-like reaction, that is, an immune complex-mediated reaction produced under conditions of excess antigens, for the second patient. We report the cases of a 52-year-old (Patient 1) and a 56-year-old (Patient 2) female patients, followed for severe AD with multiple previous treatment failures. [Extracted from the article]

Background: Chronic red blood cell exchanges (RBCXs) are frequently used to prevent complications in patients with sickle cell anemia, but the scarcity of matched red blood cell packs (RBCPs) is a serious concern. The main goal of this study was to compare the number of RBCPs used during RBCXs between the Spectra Optia (SO) device (with the automatic depletion step) and the former Cobe Spectra (CSP) device.Study Design and Methods: The performances and safety of 300 SO sessions using the automatic depletion step (SO/DE) in 50 patients with sickle cell anemia under a chronic transfusion program over a 1-year period were prospectively analyzed. The numbers of RBCPs saved using this protocol compared to the SO device without depletion and to the CSP device were determined.Results: The SO/DE protocol appeared to be safe, as only 5% and 17% of the sessions were characterized by a significant decrease in blood pressure and increase in heart rate (grade 2 adverse events), respectively. Postapheresis hematocrit and fraction of cells remaining reached expected values. The SO/DE protocol required 16% fewer RBCPs compared to SO without depletion, allowing a mean saving of 12 RBCPs per patient and per year and 13% fewer compared to CSP device. Interestingly, the saving was more important for patients with high total blood volume and/or high preapheresis hematocrit.Conclusion: The SO/DE protocol is an efficient, safe and cost-effective procedure for patients with sickle cell anemia under a chronic transfusion program. [ABSTRACT FROM AUTHOR]

Background Ivermectin ( IVM) is widely used in both human and veterinary medicine to treat parasitic infections. Recent reports have suggested that IVM could also have anti-inflammatory properties. Methods Here, we investigated the activity of IVM in a murine model of atopic dermatitis ( AD) induced by repeated exposure to the allergen Dermatophagoides farinae, and in standard cellular immunological assays. Results Our results show that topical IVM improved allergic skin inflammation by reducing the priming and activation of allergen-specific T cells, as well as the production of inflammatory cytokines. While IVM had no major impact on the functions of dendritic cells in vivo and in vitro, IVM impaired T-cell activation, proliferation, and cytokine production following polyclonal and antigen-specific stimulation. Conclusion Altogether, our results show that IVM is endowed with topical anti-inflammatory properties that could have important applications for the treatment of T-cell-mediated skin inflammatory diseases. [ABSTRACT FROM AUTHOR]

To cite this article: Rozieres A, Vocanson M, Rodet K, Benetiere J, Bienvenu J, Berard F, Hennino A, Nicolas J-F. CD8+ T cells mediate skin allergy to amoxicillin in a mouse model. Allergy 2010; 65: 996–1003. Background: Delayed allergic skin reactions to drugs are common iatrogenic diseases mediated by activation of specific T cells in the skin. Methods: To better understand the role of T cells in these diseases, we developed a mouse model of drug allergy induced by skin sensitization to amoxicillin (amox), a penicillin antibiotic frequently involved in delayed drug allergy. Results: Whereas wild-type mice could not be sensitized to amox, CD4+ T-cell-deficient mice developed an amox-specific allergic skin response, mediated by IFN-γ-producing CD8+ T cells. Amox-specific CD8+ T cells, induced in lymphoid organs at a high frequency during sensitization, were recruited in the skin upon challenge. CD8+ T cells were effectors of the allergic skin reaction to amox as in vivo treatment with depleting anti-CD8 mAbs abrogated the skin inflammatory reaction and as purified CD8+ T cells could adoptively transfer the allergic response to naive recipients. Conclusion: CD8+ T cells mediate penicillin skin allergy. [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis (ACD), one of the commonest occupational diseases, is a T-cell-mediated skin inflammation caused by repeated skin exposure to contact allergens, i.e. nonprotein chemicals called haptens. Allergic contact dermatitis, also referred to as contact hypersensitivity, is mediated by CD8+ T cells, which are primed in lymphoid organs during the sensitization phase and are recruited in the skin upon re-exposure to the hapten. Subsets of CD4+ T cells endowed with suppressive activity are responsible for both the down-regulation of eczema in allergic patients and the prevention of priming to haptens in nonallergic individuals. Therefore, ACD should be considered as a breakdown of the skin immune tolerance to haptens. Recent advances in the pathophysiology of ACD have demonstrated the important role of skin innate immunity in the sensitization process and have revisited the dogma that Langerhans cells are mandatory for CD8+ T-cell priming. They have also introduced mast cells as a pivotal actor in the magnitude of the inflammatory reaction. Finally, the most recent studies address the nature, the mode and the site of action of the regulatory T cells that control the skin inflammation with the aim of developing new strategies of tolerance induction in allergic patients. [ABSTRACT FROM AUTHOR]

Severe cutaneous adverse reactions to drugs (SCARs) are rare but life-threatening delayed allergies. While they primarily affect the skin, they can also affect internal organs. Accordingly, they present with diverse clinical symptoms that vary not only between SCARs subtypes but also among patients. Despite the availability of topical and systemic treatments, these only address the symptoms and not the cause. To develop more effective therapies, it is necessary to elucidate the complexity of the pathophysiology of SCARs in relation to their severity. In line with the new type IV hypersensitivity reactions nomenclature proposed by the European Academy of Allergy and Clinical Immunology (EAACI), this review highlights the current insights into the intricate immune mechanisms engaged, the interplay between the culprit drug and genetic predisposition in drug presentation mechanisms, but also how external factors, such as viruses, are implicated in SCARs. Their relevance to the development of targeted medicine is also discussed., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Tissue-resident memory T (T RM ) cells are detrimental in allergic contact dermatitis (ACD), in which they contribute to the chronicity and severity of the disease., Methods: We assessed the impact of a standard topical corticosteroid (TCS) treatment, triamcinolone acetonide (TA), on the formation, maintenance and reactivation of epidermal T RM cells in a preclinical model of ACD to 2,4-dinitrofluorobenzene. TA 0.01% was applied at different time points of ACD response and we monitored skin inflammation and tracked CD8+ CD69+ CD103+ T RM by flow cytometry and RNA sequencing., Results: The impact of TA on T RM formation depended on treatment regimen: (i) in a preventive mode, that is, in sensitized mice before challenge, TA transiently inhibited the infiltration of effector T cells and the accumulation of T RM upon hapten challenge. In contrast, (ii) in a curative mode, that is, at the peak of the ACD response, TA blocked skin inflammation but failed to prevent the formation of T RM . Finally, (iii) in a proactive mode, that is, on previous eczema lesions, TA had no effect on the survival of skin T RM , but transiently inhibited their reactivation program upon allergen reexposure. Indeed, specific T RM progressively regained proliferative functions upon TA discontinuation and expanded in the tissue, leading to exaggerated iterative responses. Interestingly, T RM re-expansion correlated with the decreased clearance of hapten moieties from the skin induced by repeated TA applications., Conclusions: Our results demonstrate that TCS successfully treat ACD inflammation, but are mostly ineffective in impeding the formation and expansion of allergen-specific T RM , which certainly restricts the induction of lasting tolerance in patients with chronic dermatitis., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic., Methods: To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants., Results: A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation., Conclusion: These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)