Abstract

Total serum IgE result from the combination of specific and non-specific pools. High specific/total IgE ratio may reflect high level of allergen-specific IgE on mast cells. No data regarding its applications to drug allergies is available. One hundred seventy-one patients with a history of immediate reactions to β-lactams, confirmed by positive skin testing, and 122 control subjects tolerant to β-lactams, were studied. CAP System was used for the detection of serum total and specific IgE antibodies. The specific/total IgE ratio was tested for diagnostic accuracy compared with conventional criteria. We finally performed a simulation study to expand our investigation of the performance of the specific/total IgE ratio index in a scenario in which the new CAP detection threshold is lowered further. Specific/total IgE ratio values ≥0.002 were observed more frequently in reactive than in controls. Seventy-four of 80 subjects with values ≥0.002 were allergic to β-lactams, yielding a positive predictive value of 92.5%. The application of specific/total IgE ratio significantly improves the positive likelihood ratio and the overall diagnostic performance. In addition, we showed the capability of this new criterion to identify true reactive patients even among subjects with high levels of total IgE (>200 kU/L). Significant increase in both receiver operator characteristic (ROC) curve and sensitivity were observed in imputed case of the simulation study. The β-lactams-specific/total IgE ratio may be an additional index compared to the common criterion of positivity to a single hapten in the allergological work-up of patients with β-lactams immediate adverse reactions.

Highlights

  • In order to assess the impact of each hapten on ratio diagnostic performance, we excluded it from ratio computation and compared Area Under the Curve (AUC)

  • Our study shows that the ratio of the sum of β-lactam specific to total IgE is able to improve the diagnostic performance of CAP assay in the identification of reactive patients

  • The elevated value of the specific/total IgE ratio observed in our β-lactams reactive patients is in accordance with the biological background of the mast cells/basophils IgE-induced activation

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Summary

Introduction

We evaluated the distribution of specific/total IgE ratio values in patients with a confirmed history of immediate adverse reaction to β-lactams, compared to negative control subjects. The diagnostic performance of a CAP test for β-lactams (cut-off positivity >0.10 kUA/l for at least one hapten) is maximized for patients with low to moderate total IgE levels (

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