Respiratory microbiome dysbiosis in STAT3 hyper-IgE syndrome (Job syndrome)
- 1Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill
- 2National Institutes of Allergy and Infectious Diseases, National Institutes of Health
Abstract
STAT3 hyper-IgE syndrome (STAT3-HIES), historically known as Job syndrome, is a rare primary immunodeficiency caused by dominant-negative mutations in STAT3. STAT3-HIES is characterized by impaired mucosal immunity, connective tissue abnormalities, and recurrent cutaneous and pulmonary infections. Although STAT3-dependent immune and epithelial pathways are central to airway host defense, the respiratory microbiome in STAT3-HIES remains poorly defined. To address this question, we profiled upper and lower respiratory tract microbiomes using 16S rDNA gene sequencing of oral rinse samples from eight STAT3-HIES participants and eight matched healthy controls, and bronchoalveolar lavage fluid (BALF) samples from eight STAT3-HIES participants and six healthy controls that passed sequencing quality thresholds. Oral rinse samples from STAT3-HIES participants showed lower phylogenetic diversity and significantly altered microbial community structure compared with controls. In BALF, α-diversity was comparable between groups, but β-diversity differed significantly, indicating altered lower airway microbial community composition in STAT3-HIES. Differential abundance analysis identified enrichment of the genus Rothia in STAT3-HIES BALF, and Rothia relative abundance positively correlated with BALF IL-1β, IL-1RA, and IL-8. Although limited by cohort size, these findings provide the first characterization of respiratory microbiome alterations in STAT3-HIES and suggest that impaired STAT3-dependent immune pathways may influence airway microbial ecology and inflammatory responses.
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BibTeX
@article{roca2026respiratory,
title = {{Respiratory microbiome dysbiosis in STAT3 hyper-IgE syndrome (Job syndrome)}},
author = {Cristian Roca and Matthew A. Greenwald and Bryan T. Zorn and Ling Sun and Gang Chen and Alexandra F. Freeman and Richard C. Boucher and Kenneth N. Olivier and Matthew C. Wolfgang},
journal = {Orphanet Journal of Rare Diseases},
year = {2026},
month = jul,
doi = {10.1186/s13023-026-04508-x},
url = {https://doi.org/10.1186/s13023-026-04508-x},
note = {CC BY},
}
RIS
TY - JOUR
TI - Respiratory microbiome dysbiosis in STAT3 hyper-IgE syndrome (Job syndrome)
AU - Cristian Roca
AU - Matthew A. Greenwald
AU - Bryan T. Zorn
AU - Ling Sun
AU - Gang Chen
AU - Alexandra F. Freeman
AU - Richard C. Boucher
AU - Kenneth N. Olivier
AU - Matthew C. Wolfgang
PY - 2026
DA - 2026/07/01
JO - Orphanet Journal of Rare Diseases
DO - 10.1186/s13023-026-04508-x
UR - https://doi.org/10.1186/s13023-026-04508-x
AB - STAT3 hyper-IgE syndrome (STAT3-HIES), historically known as Job syndrome, is a rare primary immunodeficiency caused by dominant-negative mutations in STAT3. STAT3-HIES is characterized by impaired mucosal immunity, connective tissue abnormalities, and recurrent cutaneous and pulmonary infections. Although STAT3-dependent immune and epithelial pathways are central to airway host defense, the respiratory microbiome in STAT3-HIES remains poorly defined. To address this question, we profiled upper and lower respiratory tract microbiomes using 16S rDNA gene sequencing of oral rinse samples from eight STAT3-HIES participants and eight matched healthy controls, and bronchoalveolar lavage fluid (BALF) samples from eight STAT3-HIES participants and six healthy controls that passed sequencing quality thresholds. Oral rinse samples from STAT3-HIES participants showed lower phylogenetic diversity and significantly altered microbial community structure compared with controls. In BALF, α-diversity was comparable between groups, but β-diversity differed significantly, indicating altered lower airway microbial community composition in STAT3-HIES. Differential abundance analysis identified enrichment of the genus Rothia in STAT3-HIES BALF, and Rothia relative abundance positively correlated with BALF IL-1β, IL-1RA, and IL-8. Although limited by cohort size, these findings provide the first characterization of respiratory microbiome alterations in STAT3-HIES and suggest that impaired STAT3-dependent immune pathways may influence airway microbial ecology and inflammatory responses.
SN - 1750-1172
ER -