In vitro Tests of T-Cell-Mediated Drug Hypersensitivity

Abstract

In clinical practice, side effects of drugs are a major problem. A broad range of drugs can elicit many different immunemediated diseases with distinct pathomechanisms. In this chapter, we focus on current in vitro techniques for the diagnosis of T-cell-mediated drug hypersensitivity. Specifically, we discuss the most recent findings regarding the diagnosis of T-cell-mediated drug hypersensitivity reactions that can be applied to the development of new tests which would enable a more conclusive diagnosis.

Drug‐specific in vitro release of IL‐2, IL‐5, IL‐13 and IFN‐γ in patients with delayed‐type drug hypersensitivity

“…Assaying cytokine secretion patterns has previously been postulated as a promising in vitro read‐out system of drug hypersensitivity (21), and several studies have suggested to measure IL‐5 or IFN‐γ in the supernatant of drug‐stimulated PBMC (10, 14, 22). The reported patterns of cytokine secretion were proposed to be more sensitive than proliferation assays and to be better correlated with the pathogenetic events.…”

In vitro diagnosis of T cell‐mediated drug allergy

“…Because their role in the effector phase of the immune response, cytokines were considered as a promising in vitro readout system in diagnosis of drug hypersensitivity [66]. Their early production after T cell activation would also shorten the incubation time to 48-72 h. The measurement of cytokine production can be performed in the cell culture supernatant by enzyme-linked immunoassays, such as the ELISA or the enzyme-linked immunospot technique; intracellularly by flow cytometry with fluorescent-conjugated monoclonal antibodies; as well as by molecular techniques like PCR or competitive reverse transcription PCR detecting the gene expression level of secreted cytokines.…”

CD69 upregulation on T cells as an in vitro marker for delayed‐type drug hypersensitivity

“…In vitro tests have the advantages of being safe by avoiding new or recall sensitizations or other adverse drug effects and of providing insight into the underlying pathomechanisms. While the LTT is used to diagnose T‐cell‐mediated drug hypersensitivity in vitro (15), it imposes technical problems (14, 31). Here, we show that the measurement of CD69 upregulation on T cells is a promising alternative.…”

“…As many drug‐hypersensitivity reactions are not mediated by drug‐specific IgE antibodies but by drug‐reactive T cells, these tests often fail at identifying the culprit drug. Several studies have shown that drug‐reacting T cells exist in the affected tissue and peripheral blood of patients suffering from all four types of allergic reactions (3–12), that they have a high frequency in the peripheral blood of patients in remission, and are present even 12 year after the acute reaction (13), implying that drug‐reactive T cells might be detectable by in vitro tests using T‐cell activation, cytokine production or proliferation as parameters (14).…”