Low IgE Is Insufficiently Sensitive to Guide Genetic Testing of STAT3 Gain-of-Function Mutations.

Abstract

To the Editor: We read with great interest the letter by Johnson et al. on the value of below reference serum IgE concentration in the diagnosis of hypermorphic or gain-of-function (GoF)1 signal transducer and activator of transcription 3 ( STAT3 ) mutations (MIM: 615952) (1). As noted by the authors, previously published literature does not support the proposal that IgE <2 kU/mL would be reliable in differentiating individuals in need of genetic testing (2–4). Johnson et al. report total IgE concentrations in kilounits per liter, equivalent to International units per milliliter (5). Based on 6 patients with STAT3 GoF, they suggest that this feature could be used to guide genetic testing. Because we collectively follow a large cohort either carrying previously published activating STAT3 mutations or novel mutations with gain of STAT3 luciferase reporter activity, we decided to collect and measure IgE concentrations in this cohort to validate the suggestion of Johnson et al. To test the notion …