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Intermediate phenotypes in patients with autosomal dominant hyper-IgE syndrome caused by somatic mosaicism

  • 0Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md., USA.
The Journal of Allergy and Clinical Immunology +

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April 30, 2013

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April 30, 2013

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Summary

This summary is machine-generated.

Somatic mosaicism in signal transducer and activator of transcription 3 (STAT3) causes milder autosomal dominant hyper-IgE syndrome (AD-HIES). This finding suggests candidiasis in AD-HIES is not solely due to low TH17 cells and that neutrophil chemotaxis is normal.

Area Of Science

  • Immunology
  • Genetics
  • Molecular Biology

Background

  • Autosomal dominant hyper-IgE syndrome (AD-HIES) is a primary immunodeficiency typically caused by mutations in STAT3.
  • Understanding the full spectrum of STAT3 mutations, including somatic mosaicism, is crucial for elucidating AD-HIES pathogenesis.

Observation

  • Two subjects presented with intermediate AD-HIES phenotypes, indicating a potential role for somatic mosaicism.
  • Analysis revealed preserved T-helper 17 (TH17) cell compartments and normal CD8 cells despite the presence of STAT3 mutations.

Findings

  • STAT3 somatic mosaicism was confirmed through tissue sequencing and mosaicism percentage calculation.
  • Neutrophil chemotaxis in response to injury appeared normal in vivo, as mutant and wild-type neutrophils migrated similarly into suction blister exudate.
  • Despite preserved TH17 cells, subjects experienced mucocutaneous candidiasis, challenging existing hypotheses on AD-HIES etiology.

Implications

  • STAT3 somatic mosaicism explains milder AD-HIES phenotypes and offers a model for studying dominant STAT3 mutation effects.
  • The findings suggest that candidiasis in AD-HIES may involve mechanisms beyond reduced TH17 cell numbers.
  • Normal in vivo neutrophil chemotaxis in STAT3 mosaicism patients indicates that early inflammatory responses may be preserved.

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