Title:Cellular Tests for the Evaluation of Drug Hypersensitivity
VOLUME: 22 ISSUE: 45
Author(s):Adriana Ariza, Maria I. Montanez, Tahia D. Fernandez, James R. Perkins and Cristobalina Mayorga
Affiliation:Research Unit for Allergic Diseases, IBIMA-Regional University Hospital of Malaga, Pl. Hospital Civil, 29009 Malaga
Keywords:Basophils, diagnosis, drug hypersensitivity, IgE, in vitro tests, lymphocytes.
Abstract:The diagnosis of drug hypersensitivity reactions (DHR) is complex, with many
potential pitfalls. Although the use of clinical history and skin testing can be valuable, drug
provocation testing (DPT) remains the gold standard for many DHR. However, DPT carries
some potential risk and should not be performed for severe reactions. There is therefore a
general consensus on the need to improve in vitro tests to achieve safe and accurate diagnosis
of DHR.
A range of in vitro approaches can be applied depending on the type of reaction and the
immunological mechanism involved, i.e. IgE- or T-cell-mediated. However, commercially
available tests only exist for a handful of drugs, and only for drugs that provoke IgEmediated
DHR. Of the cellular tests that focus on the identification of the culprit drug, the
best validated is the basophil activation test used for evaluating IgE-mediated reactions. For
T-cell-mediated DHR, the lymphocyte transformation test and enzyme-linked immunosorbent
spot appear to be the most promising. However, these tests often show low sensitivity. Despite their current
drawbacks, in vitro tests can complement in vivo testing and further work in this area will be crucial to improve
our current arsenal of tools for the detection and assessment of DHR. For this, the use of appropriate and relevant
drug metabolites as well as other factors that can amplify the cell response as well as the use of multiple tests in
concert key to improving in vitro diagnosis. Such improvements will be crucial to diagnose patients with severe
reactions for whom DPT cannot be performed.
