Basophil Activation in Immediate Drug Hypersensitivity Reactions and Basophil Activation Test (BAT)

Abstract

In the basophil activation test (BAT), the expression of the degranulation marker lysosomal-associated membrane glycoprotein-3, also termed as CD63, or upregulation of CD203c is determined. Degranulation is the fusion of specific intracellular vesicles filled with preformed mediators, which are the so-called granules, with the plasma membrane and the transition of CD63 from inside out. The result is a sudden and pronounced rise, i.e., log shift, of the fluorescence intensity signal in the detection of surface CD63 molecule. Concomitantly, the upregulation of CD203c has been observed; this can be detected as a significant increase in the mean fluorescence intensity signal of the CD203c detection antibody. The most common identification strategies use surface IgE, eotaxin CC chemokine receptor 3, the interleukin-3 receptor alpha chain CD123, the prostaglandin D2 receptor CRTH-2, or the basophilspecific ectonuclease CD203c. The usefulness of BAT in immediate drug hypersensitivity reactions is highly variable and dependent on the drug and its capacity to spontaneously conjugate to serum proteins. Stimulation with pure solutions of the parent drug or metabolites thereof versus drug-protein conjugates may influence the sensitivity and specificity of the BAT. Other influencing factors are as follows: the selection of stimulants or of identification and activation markers, the protocol for stimulation, strategies for gating, and the definition of the cut-off. The BAT is helpful to detect immediate drug hypersensitivity reactions to beta-lactam antibiotics, neuromuscular blocking agents, radiocontrast media, platinum-containing chemotherapeutics, analgesics, and biologicals or quinolone. In general, although there is a good correlation among the skin test, drug provocation test, and BAT; BAT has proven to be useful to complement in vivo tests.