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Predominance of IL-5-secreting drug-specific T cells in subgroups of patients with drug-induced delayed-type hypersensitivity reaction

Background

Drug hypersensitivity reactions (DHRs) can be classified into IgE-induced, immediate type and T-cell mediated, delayed-type reactions. While the former are considered as Th2-driven immune responses characterized by IL-5-secretion, the later are regarded as mainly provoked by IFN-gamma-producing Th1 cells. However, it has been suggested that delayed-type DHRs could also be elicited by IL-5 or a mixed T cell cytokine pattern.

Methods

We sought to characterize drug-specific T cell subpopulations in patients with delayed-type DHRs to beta-lactam antibiotics by enzyme-linked immunospot (ELISPOT) assay, a sensitive technique to detect antigen-specific cytokine-producing cells. Peripheral blood was drawn from eight patients who had experienced maculopapular exanthema as a clinical manifestation of a DHR against beta-lactam antibiotics (penicillin, amoxicillin or cefuroxim), which was confirmed by skin patch-test. The occurrence and frequencies of drug-specific IL-5-, IFN-gamma- and IL-10-producing T cells were analyzed by ELISPOT assay and compared to ten healthy controls without history of delayed-type DHRs.

Results and conclusion

As expected, ELISPOT analysis of peripheral blood mononuclear cells (PBMC) revealed increases in drug-specific IFN-gamma-producing T cells. However, in a subgroup of patients with delayed-type DHRs, augmented numbers of drug-specific IL-5-secreting T cells were observed, regardless which drug was taken. Of note, IL-10 positive T cells were not decreased in drug-allergic patients when compared with healthy controls. Our results show that DHRs are characterized by distinct patterns of cytokine-secreting lymphocytes which resemble either Th1, Th2 or a mixed type of Th cells. Thus, determining both IFN-gamma- and IL-5-positive (but not IL-10-producing) cells by ELISPOT assay increases the sensitivity in detecting drug-specific T cells. This may help diagnosing drug-allergy in patients with suspected DHRs negative by other conventional allergy tests.

Author information

Correspondence to Wolfgang Pfützner.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Keywords

  • Peripheral Blood Mononuclear Cell
  • Amoxicillin
  • Hypersensitivity Reaction
  • ELISPOT Assay
  • Drug Hypersensitivity