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).
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.
Ten patients were detected to have mutations in DOCK8 gene and autosomal recessive HIES (AR-HIES); and four patients were found with STAT3 mutation and autosomal dominant HIES (AD-HIES).
This article focuses on loss of function STAT3 mutations causing autosomal-dominant hyper-IgE syndrome and dedicator of cytokinesis 8 deficiency, with discussion of other more recently described diseases.
Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency presenting as two forms including autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES), which are mainly caused by mutations in STAT3 and DOCK8, respectively.
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.
This study was undertaken to functionally characterize neutrophils in STAT3-deficient HIES patients and to analyze whether the patients` eosinophilia affects the neutrophil phenotype in S. aureus infection.
Patients with defects in the Th17/IL-17 axis, such as patients harboring loss-of-function STAT3 mutations (autosomal-dominant hyper IgE syndrome; AD-HIES) present with recurrent oral fungal infections.
Loss-of-function mutations in the signal transducer and activator of transcription 3 gene (<i>stat3</i>) result in autosomal dominant hyper-IgE syndrome (AD-HIES), a condition in which patients have recurrent debilitating infections, including frequent pneumococcal and staphylococcal pneumonias.
STAT2 deficiency has been described in 5 family members and is characterized by selective susceptibility to viral infections, whereas STAT3 loss-of-function (LOF) mutations are causative of the autosomal-dominant hyper-IgE syndrome (HIES), a condition that is characterized by cutaneous and respiratory infections in association with mucocutaneous candidiasis, eczema, skeletal and connective tissue abnormalities, eosinophilia, and high levels IgE.
STAT 3 deficiency (autosomal dominant hyper immunoglobulin E syndrome (AD-HIES)) is a primary immunodeficiency disorder with multi-organ involvement caused by dominant negative signal transducer and activator of transcription gene 3 (STAT3) mutations.
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.
Thus, most AD-HIESSTAT3 mutations are destabilizing; agents that modulate chaperone protein function improve STAT3 stability and activity in T cells and may provide a specific treatment.
We have demonstrated previously that patients and mice with signal transducer and activator of transcription 3 (STAT3) mutations (autosomal dominant hyper-IgE syndrome [AD-HIES]) are partially protected from anaphylaxis.
Autosomal dominant hyper-IgE syndrome (AD-HIES) is a primary immunodeficiency mainly caused by mutations in STAT3, a signalling molecule implicated in the development of appropriate immune responses.
Autosomal dominant hyper-IgE syndrome (AD-HIES) is included among primary immunodeficiencies, and results from heterozygous mutations in the signal transduction and activator of transcription 3 (STAT3) gene.
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.