The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations

Abstract

Background 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. Methods Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed. Results The 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. Conclusion We 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.

Defective Toll-Like Receptors Driven B Cell Response in Hyper IgE Syndrome Patients With STAT3 Mutations

“…Despite having mutations in different domains of STAT3, all patients showed similar kinds of defective B cell function ex-vivo results. It was reported that these mutations were all LOF STAT3 mutations and led to impaired STAT3 signaling (34,35), which might have a similar effect on patients' B cell function.…”

Inherited human ZNF341 deficiency

“…The clinical phenotype of patients with AR ZNF341 deficiency is essentially a phenocopy of AD STAT3 deficiency. However, it has milder consequences, as illustrated by the median HIES NIH (National Institutes of Health) score of 28.5 for these patients, as opposed to 64 for patients with AD STAT3 deficiency ( Table 1 ) [ 18 , 19 , 25 – 33 ]. Atopic dermatitis was the most common clinical presentation of patients with ZNF341 deficiency, present in all patients reported, a proportion similar to that for patients with STAT3 deficiency (> 90%).…”