RESPONSES TO PNEUMOCOCCAL INFECTION AND IMMUNIZATION IN MICE WITH A STAT3 MUTATION RECAPITULATING AUTOSOMAL DOMINANT HYPER IGE SYNDROME (AD-HIES)

Hyper-immunoglobulin E syndromes (HIES) including compound primary immunodeficiency and nonimmunological abnormalities are characterized by extremely high serum IgE levels, eosinophilia, eczema, susceptibility to infections, distinctive facial appearance, retention of deciduous teeth, cyst-forming pneumonias, and skeletal abnormalities. Itis reported that some cases of familial HIES are relative to autosomal dominant or recessive inheritance, but most cases are sporadic, and result from mutations in the human signal transducer and activator of transcription 3 (STAT3) gene. In this paper, we firstly report a young man diagnosed of Hyper-IgE syndrome with STAT3 mutation in Mainland China, and investigate the autosomal dominant trait of his family members.

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On Two Cases with Autosomal Dominant Hyper IgE Syndrome: Importance of Immunological Parameters for Clinical Course and Follow-Up

Case Reports in Immunology ◽

10.1155/2020/6694957 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Snezhina Mihailova Kandilarova ◽

Spaska Stoyneva Lesichkova ◽

Nevena Todorova Gesheva ◽

Petya Stefanova Yankova ◽

Nedelcho Hristov Ivanov ◽

...

Keyword(s):

Autosomal Dominant ◽

Clinical Symptoms ◽

Clinical Course ◽

Dna Binding Domain ◽

Disease Course ◽

Immunological Parameters ◽

Laboratory Findings ◽

Hyper Ige Syndrome ◽

Stat3 Mutation

Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare disease described in 1966. It is characterized by severe dermatitis, a peculiar face, frequent infections, extremely high levels of serum IgE and eosinophilia, all resulting from a defect in the STAT3 gene. A variety of mutations in the SH2 and DNA-binding domain have been described, and several studies have searched for associations between the severity of the clinical symptoms, laboratory findings, and the type of genetic alteration. We present two children with AD-HIES–a girl with the most common STAT3 mutation (R382W) and a boy with a rare variant (G617E) in the same gene, previously reported in only one other patient. Herein, we discuss the clinical and immunological findings in our patients, focusing on their importance on disease course and management.

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Recurrent Skin and Lung Infections in Autosomal Dominant Hyper IgE Syndrome with Transactivation Domain STAT3 Mutation

Case Reports in Immunology ◽

10.1155/2014/136752 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Chad J. Cooper ◽

Sarmad Said ◽

German T. Hernandez

Keyword(s):

Mutation Analysis ◽

Autosomal Dominant ◽

Genetic Disorder ◽

Genetic Mutation ◽

Entire Body ◽

Transactivation Domain ◽

Gastrointestinal Infections ◽

Hyper Ige Syndrome ◽

Stat3 Mutation ◽

Lung Infections

Background. Hyper IgE is a rare systemic disease characterized by the clinical triad of high serum levels of IgE (>2000 IU/mL), eczema, and recurrent staphylococcal skin and lung infections. The presentation of hyper IgE syndrome is highly variable, which makes it easy to confuse the diagnosis with that of severe atopy or other rare immunodeficiency disorders.Case Report. A 23-year-old Hispanic presented with history of frequent respiratory and gastrointestinal infections as a child and multiple episodes of skin and lung infections (abscess) withStaphylococcus aureusthroughout his adult life. He had multiple eczematous lesions and folliculitis over his entire body, oral/esophageal candidiasis, and retention of his primary teeth. The IgE was elevated (>5000 IU/mL). Genetic mutation analysis revealed a mutation affecting the transactivation domain of the STAT3 gene.Conclusion. The hallmark of hyper IgE syndrome is serum IgE of >2000 IU/mL. Hyper IgE syndrome is a genetic disorder that is either autosomal dominant or recessive. A definite diagnosis can be made with genetic mutation analysis, and in this case, it revealed a very rare finding of the transactivation domain STAT3 mutation. Hyper IgE syndrome is a challenge for clinicians in establishing a diagnosis in suspected cases.

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TWO PATIENTS OF AUTOSOMAL DOMINANT STAT3 DEFICIENCY AND HYPER-IGE SYNDROME: MOLECULAR AND CLINICAL FEATURES

10.26226/morressier.57bc1758d462b80290b4d224 ◽

2016 ◽

Author(s):

Maria Reyes Jimenez Leon

Keyword(s):

Clinical Features ◽

Autosomal Dominant ◽

Hyper Ige Syndrome

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Faculty Opinions recommendation of Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1103840.559969 ◽

2008 ◽

Author(s):

Joseph Mizgerd

Keyword(s):

Cell Differentiation ◽

Autosomal Dominant ◽

Hyper Ige Syndrome

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Very Elevated IgE, Atopy, and Severe Infection: A Genomics-Based Diagnostic Approach to a Spectrum of Diseases

Case Reports in Immunology ◽

10.1155/2021/2767012 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

A. Chin ◽

S. Balasubramanyam ◽

C. M. Davis

Keyword(s):

Autosomal Dominant ◽

Severe Infection ◽

Severe Atopic Dermatitis ◽

Genomic Testing ◽

Atopic Diseases ◽

Variants Of Unknown Significance ◽

Hyper Ige Syndrome ◽

Heterozygous Variant ◽

Unknown Significance ◽

Multiple Variants

Elevated IgE has been long recognized as an important clinical marker of atopy but can be seen in a myriad of conditions. The discovery of autosomal dominant STAT3 deficiency marked the first recognition of hyper-IgE syndrome (HIES) and the first primary immunodeficiency linked to elevated IgE. Since then, genomic testing has increased the number of defects with associated mutations causing hyper-IgE syndrome and atopic diseases with FLG, DOCK8, SPINK5, and CARD11, among others. A spectrum of recurrent infections and atopy are hallmarks of elevated IgE with significant phenotypic overlap between each underlying condition. As treatment is predicated on early diagnosis, genomic testing is becoming a more commonly used diagnostic tool. We present a 6-year-old male patient with markedly elevated IgE and severe atopic dermatitis presenting with staphylococcal bacteremia found to have a heterozygous variant in FLG (p.S3247X) and multiple variants of unknown significance in BCL11B, ZAP70, LYST, and PTPRC. We review the genetic defects underpinning elevated IgE and highlight the spectrum of atopy and immunodeficiency seen in patients with underlying mutations. Although no one mutation is completely causative of the constellation of symptoms in this patient, we suggest the synergism of these variants is an impetus of disease.

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