Diagnostic tests based on human basophils: potentials, pitfalls and perspectives

TY - JOUR

T1 - Diagnostic tests based on human basophils

T2 - potentials, pitfalls and perspectives

AU - Kleine-Tebbe, Jörg

AU - Erdmann, Stephan

AU - Knol, Edward F

AU - MacGlashan, Donald W

AU - Poulsen, Lars K.

AU - Gibbs, Bernhard F

N1 - Copyright (c) 2006 S. Karger AG, Basel.

PY - 2006

Y1 - 2006

N2 - Human basophils are important tools for studying immediate-type hypersensitivity reactions since they release a variety of mediators (e.g., histamine, leukotriene C4, IL-4 and IL-13) following allergen triggering. Several diagnostic tools have been introduced that measure either leukotriene production or the upregulation of surface markers (CD63 and CD203c) from these cells after antigen stimulation. However, a broad variability in basophil activity exists between different basophil donors and different antigens within one donor. This manifests itself in terms of their reactivity (maximum secretory response), based on the intracellular signaling of the basophils studied, and in terms of their sensitivity. The latter is governed by the number of IgE receptors per basophil, the ratio of antigen-specific IgE to total IgE, and by the number of cell surface antigen-specific IgE molecules for half-maximal responses, termed 'intrinsic sensitivity'. These variables give rise to shifts in the dose-response curves which, in a diagnostic setting where only a single antigen concentration is employed, may produce false-negative data. Thus, in order to meaningfully utilize the current basophil activation tests for diagnostic purposes, each allergen should be pre-evaluated separately in order to determine a suitable stimulation range. Additionally, anti-IgE or anti-FcepsilonRIalpha antibodies should serve as positive controls, bearing in mind that 10-20% of basophil donors are not responsive to IgE-mediated stimulation. Diagnostic studies using CD63 or CD203c in hymenoptera, food and drug allergy are critically discussed. Basophil-based tests are indicated for allergy testing in selected cases but should only be performed by experienced laboratories.

AB - Human basophils are important tools for studying immediate-type hypersensitivity reactions since they release a variety of mediators (e.g., histamine, leukotriene C4, IL-4 and IL-13) following allergen triggering. Several diagnostic tools have been introduced that measure either leukotriene production or the upregulation of surface markers (CD63 and CD203c) from these cells after antigen stimulation. However, a broad variability in basophil activity exists between different basophil donors and different antigens within one donor. This manifests itself in terms of their reactivity (maximum secretory response), based on the intracellular signaling of the basophils studied, and in terms of their sensitivity. The latter is governed by the number of IgE receptors per basophil, the ratio of antigen-specific IgE to total IgE, and by the number of cell surface antigen-specific IgE molecules for half-maximal responses, termed 'intrinsic sensitivity'. These variables give rise to shifts in the dose-response curves which, in a diagnostic setting where only a single antigen concentration is employed, may produce false-negative data. Thus, in order to meaningfully utilize the current basophil activation tests for diagnostic purposes, each allergen should be pre-evaluated separately in order to determine a suitable stimulation range. Additionally, anti-IgE or anti-FcepsilonRIalpha antibodies should serve as positive controls, bearing in mind that 10-20% of basophil donors are not responsive to IgE-mediated stimulation. Diagnostic studies using CD63 or CD203c in hymenoptera, food and drug allergy are critically discussed. Basophil-based tests are indicated for allergy testing in selected cases but should only be performed by experienced laboratories.

KW - Animals

KW - Basophils

KW - Humans

KW - Hypersensitivity, Immediate

KW - Immunologic Tests

U2 - 10.1159/000094495

DO - 10.1159/000094495

M3 - Journal article

C2 - 16837789

SN - 1018-2438

VL - 141

SP - 79

EP - 90

JO - International Archives of Allergy and Immunology

JF - International Archives of Allergy and Immunology

IS - 1

ER -