A previously healthy boy with severe adenovirus type 7 (HAdV-B7) pneumonia had anti–IFN-ω autoantibodies that strongly blocked IFN-ω activity in laboratory tests. Plasma from the child stopped IFN-ω from triggering a measured cellular response and removed its antiviral effect in fibroblast tests, while IFN-α2 activity remained.
The findings point to a possible contribution from the antibodies, but they do not show that the antibodies caused the pneumonia. Direct clinical evidence came from one child, while the main functional tests used cultured cells.
A severe infection in one previously healthy child
Rising adenovirus DNA indicated that the infection had disseminated through the body. The child required oxygen support through day 9 of hospitalization and was discharged after 12 days. Whole-exome sequencing found no pathogenic variants in the tested inborn-immunity genes.
The researchers tested whether the child’s plasma contained antibodies that could interfere with IFN-ω. The antibody work included ELISA, measurements of IFN-I-induced STAT1 phosphorylation in THP-1 cells, and an ISRE reporter assay used to measure interferon signaling.
The antibodies were strong and selective
The antibodies remained detectable after clinical recovery and were predominantly IgG, especially IgG1 and IgG3, with negligible IgM, IgA or IgE.
At 5% patient plasma, the activity of 50 ng/ml IFN-ω was completely abolished, but IFN-α2 signaling remained intact. In a separate reporter assay, patient plasma robustly neutralized both tested doses of IFN-ω, with complete inhibition still present at 1% plasma dilution.
Healthy-child plasma showed only partial inhibition under the reported conditions. At 10% plasma, samples from five healthy children partly inhibited 100 pg/ml IFN-ω, while samples from three children partly inhibited 10 ng/ml IFN-ω. The comparison was small and took place in a reporter assay, so it does not establish disease risk.
The child’s cells could still make the signal
To find where IFN-ω was being made during viral stimulation, the researchers compared peripheral blood mononuclear cells, or PBMCs, with fibroblasts and epithelial cells. PBMCs were identified as the principal producers.
The patient’s PBMCs retained IFN-ω and IFN-α production responses, but circulating IFN-ω was below 4.7 pg/ml, even though it was detected in most infected controls. That pattern is compatible with antibodies binding or neutralizing IFN-ω in the circulation, but it does not establish that this happened in the body.
Plasma removed IFN-ω protection in cell experiments
In primary fibroblast assays, IFN-α2 or IFN-ω was associated with higher viability after viral infection. When 1% patient plasma was added, measured IFN-ω antiviral activity was absent, while IFN-α2 activity remained.
Another test measured E1A expression in HAdV-B7-infected fibroblasts. Lower E1A expression with IFN-ω was seen with healthy-control plasma but not patient plasma. IFN-α2-associated lower viral load was observed regardless of plasma source.
A signal worth testing in more children
In screening, one of seven children with HAdV infection had anti–IFN-ω autoantibodies, or 14.3%. Seven of 455 healthy donors were positive, or 1.5%. Those numbers are descriptive, not estimates of disease risk, because the groups were small and were not designed for that question.
The authors say the case and laboratory findings support a pathogenic contribution from strongly neutralizing anti–IFN-ω autoantibodies. They suggest that screening might help identify children at risk, but say additional cases are needed.
What remains unknown
The interpretation remains limited by the study design. The clinical inference comes from one index case, while the HAdV screening group had only seven children. Key outcomes were laboratory surrogates such as STAT1 phosphorylation, reporter activity, cell viability, E1A expression and measured cytokine concentration.
The fibroblast and transformed-cell findings may not represent infected pediatric lung or other tissues. The absence of pathogenic variants in the tested genes also does not establish that every possible cause of susceptibility was excluded.
Further studies need to determine how frequently strongly neutralizing anti–IFN-ω autoantibodies occur among children with severe adenoviral disease and whether screening can improve risk stratification. The present results do not establish the antibodies’ prevalence or predictive value for severe disease.
Paper data and sources
Original title: Highly neutralizing anti–IFN-ω autoantibodies underlie severe pediatric adenovirus infection
Authors: Kang C, Ding J, Lo Y et al.
Journal/Repository: Journal of human immunity
Status: Peer-reviewed
First online: 2026-10-13
DOI: Not available
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