Epidermodysplasia verruciformis (EV) is a rare skin disorder caused by an increased susceptibility to a specific group of related human papillomaviruses. The majority of cases of this congenital disorder are associated with mutations either the gene EVER1 or EVER2.
However, the underlying cause in the remaining patients is unclear. Dr. Emmanuelle Jouanguy and researchers at INSERM in Paris now report on two patients with an immune deficiency and various infectious diseases, including persistent EV-associated human papillomavirus infections.
The Jouanguy team found that the patients both had loss-of-function of the RHOH gene, which encodes an atypical Rho GTPase that is primarily expressed in developing blood and immune cells.
The patients lacked specific populations of T cells, and those T cell present had impaired T cell receptor signaling. The team went on to model the same genetic mutation in mice, which had similar T cell defects.
Their findings uncover a new genetic risk factor for T cell deficiency and persistent EV-associated human papillomavirus infections in patients.
TITLE: Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections