Daily Mail: Rare IRF8 Immunodeficiency May Increase Susceptibility to Cancer

A woman in the UK, Sinead Owens, was diagnosed with vulvar cancer in the context of a rare genetic immunodeficiency. The patient, as well as two of her sisters, carries IRF8 deficiency — an extremely rare disorder of the immune system that increases the body’s susceptibility to infections. The medical case was reported by the Daily Mail.

IRF8 encodes a transcription factor involved in regulating the function of cells of both the innate and adaptive immune systems, including monocytes, macrophages, and dendritic cells. Impaired function of this protein can lead to insufficient development and abnormal activity of certain immune-cell populations, making it harder for the body to control some infections.

The clinical manifestations of IRF8 deficiency depend on the specific mutation and the extent of the impairment in protein function. Patients may experience recurrent viral and bacterial infections, including herpesvirus infections, respiratory tract infections, and otitis. In severe cases, the immunodeficiency may require treatment aimed at restoring immune function.

The family struggled for a long time to obtain an accurate diagnosis: the sisters’ symptoms initially appeared to be common infections. Genetic testing later revealed an abnormality in the IRF8 gene in all three women.

In severe cases, allogeneic hematopoietic stem cell transplantation may be performed. Before transplantation, patients undergo conditioning therapy, which may include chemotherapy drugs to suppress their own blood-forming and immune systems and prepare the body for engraftment of donor cells. One of the sisters has already undergone transplantation and chemotherapy.

Sinead was also diagnosed with vulvar cancer. It is noted that IRF8 deficiency may have weakened immune surveillance of tumors and contributed to their progression. However, at present, it cannot be concluded that the cancer was directly caused by the immunodeficiency.