Abstract
Background: Diagnosis of drug allergy is difficult because few methods have been validated in the literature. In the last few years, identification of T cell activation markers to assess drug allergy has been the focus of several studies. Objective: The aim of the present work was to search for CD25 and CD69 markers on T CD4+ and T CD8+ cells in drug allergy. Methods: Fourteen patients with drug hypersensitivity were enrolled in this investigation. Some patients had at least one adverse reaction to one or more suspected drugs, therefore, a total of 16 reactions and 10 drugs were investigated. Prick or patch tests were done according with the time of onset and type of the clinical manifestations. In vitro studies were performed by incubating peripheral blood mononuclear cells from patients and controls with different concentrations of the suspicious drugs for 72 hours. The samples were stained with fluorochrome- labelled monoclonal antibodies against CD69, CD25, CD4 and CD8 molecules and analyzed by flow cytometry. Results: Statistical differences were found at medium and high drug concentrations for the CD4+CD69+ marker (p ≤ 0.05), at the lowest drug concentration for the CD4+CD25+ and CD8+CD69+ markers (p ≤ 0.05) and at the highest drug concentration for the CD8+CD25+ marker (p<0.01) when samples from patients were compared to controls. One or both the markers were upregulated in 3 patients who presented positive results in prick test. Four out of six patients who presented positive patch test showed upregulation of one or both the activation markers. For instance, a patient who suffered from pruritus after thediclofenac and ASA ingestion showed a positive prick test for both drugs and presented upregulation of CD69 on CD4+ cells. Another patient who had presented contact dermatitis to rifamycin showed upregulation of CD69 on CD4+ cells, and CD25 on CD4+ and CD8+ cells. Conclusion: Our data reinforce the use of CD69 and CD25 on both CD4+ and CD8+ T cells in order to investigate drug allergy.
Highlights
Drug hypersensitivity reactions (DHR) account for approximately 15% of all adverse drug reactions [1], can be life threatening, require or prolong the period of hospitalization and entail changes in drug prescription [2]
Drug allergy was classified according to the Naranjo adverse drug reactions probability scale [15]
NSAIDs are frequently related to non- allergic reactions, the possibility of a true IgE-mediated drug allergy cannot be excluded
Summary
Drug hypersensitivity reactions (DHR) account for approximately 15% of all adverse drug reactions [1], can be life threatening, require or prolong the period of hospitalization and entail changes in drug prescription [2]. A conclusive laboratory diagnosis of drug allergy that confirms the clinical symptoms and identifies its causative agent still remains a major challenge in daily clinical practice [7]. Skin tests, such as patch, prick and intradermal tests (IDT) may present low sensitivity in patients with a clear history of DHR [5,7]. Provocation oral tests are considered to be the gold standard in drug allergy, sometimes they are not well accepted by physicians and patients due to the risk of causing severe reactions [1,8]. In the last few years, identification of T cell activation markers to assess drug allergy has been the focus of several studies
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