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17-11-2011 | Genetics | Article

STAT6 gene linked to adverse reactions following VV vaccination


Free abstract

MedWire News: US researchers have identified a gene that may help explain why patients with atopic dermatitis (AD) and a history of eczema herpeticum (EH) are at risk for developing viral skin infections.

AD is a genetically complex and chronic inflammatory skin disease, which is characterized by a defective skin barrier. Some patients with AD show bacterial and disseminated viral skin infections, such as EH.

Donald Leung (National Jewish Health, Denver, Colorado) and co-authors found that a gene known as the active signal transducer and activator of transcription (STAT)6 gene plays a key role in increasing the spread of viral infections in the skin of patients with AD who have a history of EH.

The findings are of importance, as they explain why some patients with AD develop severe adverse events following vaccination with the Vaccinia virus (VV) for smallpox.

For the study, the researchers obtained skin biopsy specimens from 55 patients with active AD (ADEH-), 36 patients with a history of AD but no currently active disease, 20 patients with AD and a history of EH (ADEH+), 38 asthma patients, 36 psoriasis patients, and 35 healthy individuals without a history of skin disease.

Following exposure of all skin samples to VV, the team found that VV gene and protein expression were significantly increased in the skin of ADEH+ patients compared with all other groups.

Further analysis of the skin samples showed that increased expression of the inflammatory mediators interleuki-4 and -13 enhanced viral replication.

Leung and team then tested their findings in transgenic mice with an active STAT6 gene, and found that these mice were more likely to die and present skin lesions after exposure to VV than mice without an active STAT6 gene.

Significant associations were seen between various mutations in STAT6 and EH and production of interferon-gamma, a protein involved defense against viral and bacterial infections.

Specifically, the team found that one specific mutation was more common in ADEH+ patients compared with ADEH- patients, at 24.9 versus 9.2%. This suggests that the observed mutation may confer susceptibility to developing ADEH and have a functional effect on disease.

The findings are published in the Journal of Allergy and Clinical Immunology.

By Ingrid Grasmo

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