Whole-exome sequencing analysis using her peripheral blood revealed a heterozygous mutation in the STAT3 gene, which is related to autosomal dominant hyper-immunoglobulin E syndrome (AD-HIES).
Mutations in STAT3 cause autosomal dominant HIES (Job's syndrome), which is unique in its diversity of connective tissue, skeletal, and vascular abnormalities.
Autosomal dominant HIES has been shown to be mainly due to STAT3 mutations and additionally results in connective tissue, skeletal, vascular and dental abnormalities.
Job syndrome or autosomal dominant hyper IgE syndrome because of heterozygous loss-of-function mutations with dominant negative effect in signal transducer and activator of transcription-3 is the prototype of these disorders.
Since STAT-3 plays a role in B cell development and differentiation, we analyzed memory B cells in 20 patients with HIES, 17 of which had STAT-3 mutations.
The majority of autosomal dominant HIES (AD HIGE) is due to hypomorphic mutations in the signal transducer and the activator of transcription 3 (STAT3) gene.
Patients with autosomal-dominant hyper-IgE syndrome (AD-HIES) carry dominant-negative STAT3 mutations and are susceptible to a variety of bacterial and fungal infections.
Autosomal dominant HIES (AD-HIES) is a primary immunodeficiency caused by dominant negative mutations in STAT3 clustered in the DNA binding and SH2 domains.
Successful haploidentical donor hematopoietic stem cell transplant and restoration of STAT3 function in an adolescent with autosomal dominant hyper-IgE syndrome.
According to the Grimbacher score the patient was likely to have AD-HIES and a novel heterozygous STAT3 mutation (c.1110-3C>A), causing a splice error, was identified.
Autosomal dominant hyper-IgE syndrome (AD-HIES) or Job's syndrome is a primary immunodeficiency with a wide array of clinical features caused by dominant negative mutations in STAT3.
This study determined mechanisms for this protection and compared this to mice with myeloid-specific STAT3-deficiency (LysMcre/STAT3(flox); gp130(757F/F) LysMcre/STAT3(flox)).
The autosomal recessive hyper-IgE syndrome (HIES) caused by dedicator of cytokinesis 8 (DOCK8) deficiency shares clinical features with autosomal dominant HIES because of signal transducer and activator of transcription 3 (STAT3) mutations, including recurrent infections and mucocutaneous candidiasis, which are suggestive of T<sub>H</sub>17 cell dysfunction.
In this article, we will review how the study of STAT3 deficiency in humans and mice has highlighted nonredundant roles of STAT3, and of specific cytokines, in diverse cellular processes such as antimicrobial immunity and protection at epithelial barriers, the generation of functional humoral immune responses, bone formation, and keratinocyte biology.
By contrast, CMC is one of the few key infections in patients with autosomal dominant hyper IgE syndrome (mutations in STAT3), and in rare patients with autosomal recessive predisposition to mucocutaneous and invasive fungal infections (mutation in CARD9).