29 September 2020
Deciphering the relevance of a new gene for Hyper IgE syndrome
Published online 27 June 2018
Scientists illuminate genetics underlying a rare disorder of the immune system.
Scientists have probed the molecular and cellular basis of a form of hyper IgE syndrome, a rare immunodeficiency condition that manifests as a skin and systemic allergy combined with bacterial infection, inflammation and bone abnormalities, sharing their insights in a new research.
The hallmark of the disease is extremely elevated levels of Immunoglobulin E (IgE), antibodies that the immune system produces in response to an allergen. Mutations and deficiencies in the STAT3 gene underlie many cases of hyper IgE syndrome.
In a new paper in Science Immunology1, researchers led by Jean-Laurent Casanova, professor at the Rockefeller University, investigator at the Howard Hughes Medical Institute, and head of the St. Giles Laboratory of Human Genetics of Infectious Diseases, write that they discovered a new gene and protein, ZNF341, whose deficiency is associated with a form of the disease.
According to Casanova, this new protein is essential to the transcriptional regulation of STAT3.
“The discovery of ZNF341 deficiency simply helps the ZNF341-deficient patients because it anchors them to STAT3," says Casanova of the therapeutic implications of the study's findings. "In other words, we know now that the treatments proposed to STAT3-deficient patients can potentially be applied to ZNF341-deficient patients, because the two forms of the disease are tightly connected.”
According to the scientist, beyond hyper IgE syndrome, the discovery can illuminate understanding of a large number of allergic diseases associated with the condition. "The discovery that mutations in STAT3 and ZNF341 underlie allergy in the context of the hyper IgE syndrome is telling us that these pathways may also be affected in the context of other conditions."
- Béziat, V. et al. A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity. Sci. Immunol. 3, eaat4956 (2018).