Signal Transducer and Activator of Transcription 3 (STAT3) Variant p.K709N Causes Hyper-IgE Syndrome Likely by Impaired STAT3-Dimer Formation.

STAT3-hyper-IgE syndrome (STAT3-HIES) is an inborn error of immunity caused by heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3). In this study, we evaluate the functional relevance of a previously undescribed heterozygous STAT3 variant in a patient with clinical findings of STAT3-HIES. Flow cytometry, quantitative real-time PCR, pull-down assays, native PAGE, DNA-binding ELISA, and 3D-structural data analysis were performed.

Imported Toxigenic Corynebacterium Diphtheriae in Refugees with Polymicrobial Skin Infections, Germany, 2022.

During August-December 2022, toxigenic Corynebacterium diphtheriae was isolated from 25 refugees with skin infections and 2 refugees with asymptomatic throat colonization at a refugee reception center in Germany. None had systemic toxin-mediated illness. Of erosive/ulcerative skin infections, 96% were polymicrobial.

Intra-Household and Close-Contact SARS-CoV-2 Transmission Among Children - a Systematic Review.

The outbreak of the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a range of emergency measures worldwide. Early in the pandemic, children were suspected to act as drivers of the COVID-19 spread in the population, which was based on experiences with influenza virus and other respiratory pathogens. Consequently, closures of schools and kindergartens were implemented in many countries around the world, alongside with other non-pharmaceutical interventions for transmission control.

Retained primary teeth in STAT3 hyper-IgE syndrome: early intervention in childhood is essential.

Background: STAT3 hyper-IgE syndrome (STAT3-HIES) is a rare primary immunodeficiency that clinically overlaps with atopic dermatitis. In addition to eczema, elevated serum-IgE, and recurrent infections, STAT3-HIES patients suffer from characteristic facies, midline defects, and retained primary teeth. To optimize dental management we assessed the development of dentition and the long-term outcomes of dental treatment in 13 molecularly defined STAT3-HIES patients using questionnaires, radiographs, and dental investigations.

Impaired memory B-cell development and antibody maturation with a skewing toward IgE in patients with STAT3 hyper-IgE syndrome.

Background: Signal transducer and activator of transcription 3 hyper-IgE syndrome (STAT3-HIES) is caused by heterozygous mutations in the STAT3 gene and is associated with eczema, elevated serum IgE, and recurrent infections resembling severe atopic dermatitis, while clinically relevant specific IgE is almost absent.

Methods: To investigate the impact of STAT3 signaling on B-cell responses, we assessed lymph node and bone marrow, blood B and plasma cell subsets, somatic hypermutations in Ig genes, and in vitro proliferation and antibody production in STAT3-HIES patients and healthy controls.

Results: Lymph nodes of STAT3-HIES patients showed normal germinal center architecture and CD138 plasma cells residing in the paracortex, which expressed IgE, IgG, and IgM but not IgA.

Lung disease in STAT3 hyper-IgE syndrome requires intense therapy.

Background: Pulmonary complications are responsible for high morbidity and mortality rates in patients with the rare immunodeficiency disorder STAT3 hyper-IgE syndrome (STAT3-HIES). The aim of this study was to expand knowledge about lung disease in STAT3-HIES.

Methods: The course of pulmonary disease, radiological and histopathological interrelations, therapeutic management, and the outcome of 14 STAT3-HIES patients were assessed.

Somatic alterations compromised molecular diagnosis of DOCK8 hyper-IgE syndrome caused by a novel intronic splice site mutation.

In hyper-IgE syndromes (HIES), a group of primary immunodeficiencies clinically overlapping with atopic dermatitis, early diagnosis is crucial to initiate appropriate therapy and prevent irreversible complications. Identification of underlying gene defects such as in DOCK8 and STAT3 and corresponding molecular testing has improved diagnosis. Yet, in a child and her newborn sibling with HIES phenotype molecular diagnosis was misleading.

Key findings to expedite the diagnosis of hyper-IgE syndromes in infants and young children.

Background: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by elevated serum IgE, eczema, and recurrent infections. Despite the availability of confirmatory molecular diagnosis of several distinct HIES entities, the differentiation of HIES particularly from severe forms of atopic dermatitis remains a challenge. The two most common forms of HIES are caused by mutations in the genes STAT3 and DOCK8.