An adolescent with marked hyperimmuno-globulinemia E showing minimal change nephrotic syndrome and a STAT3 gene mutation

Abstract

We encountered a patient with marked hyperimmunoglobulinemia E who had a mutation of the signal transducer and activator of transcription 3 gene (STAT3) and developed minimal change nephrotic syndrome (MCNS). From early infancy, the patient showed repeated episodes of refractory chronic eczema accompanied by impetigo vulgaris with cicatrization, as well as otitis media. Serum IgE was markedly increased (from 4,000 to 25,000 IU/ml). The nephrotic syndrome (NS) frequently relapsed, and was alternately responsive and resistant to corticosteroids. The STAT3 mutation was heterozygous, located in exon 23 of the transactivation domain and causing A744V substitution. Presently treated with mycophenolate mofetil, the patient has less frequent MCNS recurrences. Increases in circulating Th2 cytokines and IgE combined with suppression of the Th1 cytokine interferon-γ caused by the STAT3 abnormality, presumably caused MCNS by altering the Th1/Th2 balance among T-lymphocytes. To our knowledge, this is the first report of type I hyper-IgE syndrome (HIES) showing a STAT3 gene mutation and MCNS.