Abstract
BackgroundLoss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation.MethodsTwelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed.ResultsThe median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin.ConclusionWe updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.
Highlights
Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases
STAT3-HIES was first described as Job syndrome in 1966, and it is characterized by eczematous dermatitis, recurrent skin and pulmonary abscesses and elevated serum Immunoglobulin E (IgE) levels [2,3,4]
Eleven patients were diagnosed with STAT3 LOF mutations, and one patient (P12) was diagnosed with a STAT3 GOF mutation
Summary
Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation. Loss-of-function (LOF) mutations in the signal transducer and activator of transcription 3 (STAT3) gene constitute one of the underlying causes of the autosomal dominant (AD) hyperimmunoglobulin E (IgE) syndrome (HIES). STAT3-HIES was first described as Job syndrome in 1966, and it is characterized by eczematous dermatitis, recurrent skin and pulmonary abscesses and elevated serum IgE levels [2,3,4]. There is no predominant sex or ethnicity among STAT3-HIES patients [6]. STAT3-deficient patients are more susceptible to bacterial and fungal infections and exhibit poor
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