Updated August 2026
Most people regularly inhale spores from Aspergillus fumigatus, but healthy airways usually remove them before they can persist or grow. Researchers have been investigating why this natural clearance appears to work less effectively in some people.
A study published in Nature Communications in 2018 identified a possible genetic factor. Researchers from the Manchester Fungal Infection Group studied a variant called rs35699176 in a gene known as ZNF77.
What does ZNF77 do?
ZNF77 helps regulate the airway epithelium—the layer of cells lining and protecting the breathing tubes. This lining is not simply a physical barrier. It also helps trap, remove and respond to inhaled microorganisms.
In laboratory experiments, researchers used gene editing to introduce the ZNF77 variant into human bronchial epithelial cells. Cells carrying the variant formed a less complete protective layer and produced increased amounts of proteins to which fungal spores could adhere.
Compared with ordinary airway cells, the altered cells allowed Aspergillus fumigatus spores to:
- attach more readily to the airway surface;
- begin germinating sooner;
- grow more rapidly; and
- produce a stronger inflammatory response.
What was found in people with ABPA?
The researchers also examined respiratory samples from relatively small groups of patients. Among 45 people with allergic bronchopulmonary aspergillosis (ABPA), the ZNF77 variant was found in nine of the 32 people whose sputum contained detectable Aspergillus. It was not found in the 13 people whose sputum PCR test was negative.
People carrying one copy of the variant also tended to have higher fungal loads in their airways. However, the study did not show that they had more severe asthma, poorer lung function or worse clinical outcomes.
Does this mean ZNF77 causes ABPA?
No. ABPA is a complex condition involving fungal exposure, airway disease, immune responses and probably several genetic and environmental influences. One gene variant cannot by itself explain why someone develops ABPA.
The study suggested that rs35699176 may make the airway surface more permissive to Aspergillus fumigatus. This could be one part of the process that allows the fungus to persist and trigger allergic inflammation in susceptible people.
Can patients be tested for this variant?
ZNF77 testing has not become part of routine ABPA diagnosis or treatment. The original patient groups were small, and larger studies following people over time would be needed to establish whether testing reliably predicts disease, treatment response or clinical outcomes.
The 2024 international clinical guidelines for ABPA use evidence of fungal sensitisation, total IgE, eosinophil counts, Aspergillus-specific IgG and characteristic imaging findings. They do not currently recommend ZNF77 genetic testing.
Why does the research still matter?
This study helped demonstrate that the airway lining actively influences whether Aspergillus spores are cleared or allowed to persist. It also identified fungal adhesion to airway cells as a possible target for future research.
Although the finding has not yet produced a clinical test or treatment, it remains an important example of how differences in our airway defences may contribute to susceptibility to aspergillosis.
For patients: having ABPA does not currently indicate a need for ZNF77 testing. Diagnosis and treatment should continue to be based on symptoms, blood tests, imaging, respiratory samples and specialist clinical assessment.
Further reading
- Gago S and colleagues: Lung colonization by Aspergillus fumigatus is controlled by ZNF77
- Revised international guidelines for diagnosing and treating ABPA
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