Prof. Paolo Fiorina and Dr. Francesca D”Addio tell us about the new disease the HyperTh17,discovered through their studies and publication of the new project P2X7R and Tcells Fate.

HyperTh17, is a disease that induces the condition of fragile immune system in individuals carrying a purinergic receptor 7 mutation.

The finding was published in the Journal of Clinical Investigation and is the result of a collaboration with Boston Children’s Hospital and Harvard Medical School.

Researchers have demonstrated for the first time the role of this receptor in the control of T lymphocytes during activation of the immune system under normal conditions, discovering how its mutation, which affects about 2 percent of the population, is associated with an alteration in its function that leads to hitherto unknown true immunological disease.

Mutation of the P2X7R receptor blocks the process that regulates the body’s immune response to external agents, results in the development of damaging T lymphocytes leading to a fragile state of the immune system that can have important consequences especially for patients already at risk such as transplant recipients, in whom it can lead to organ rejection, or with diseases of immunologic pathogenesis, as in diabetes.

The P2X7R mutation had been described but its role had never been clarified until now.

As stated by Prof. Paolo Fiorina, “This mutation is present in 2 percent of the general population and understanding its importance from a clinical point of view, takes on a very important relevance for our health,” says Prof. Paolo Fiorina, Associate Professor of Endocrinology at the State University of Milan and Director of the International Research Center on Type 1 Diabetes at the Romeo and Enrica Invernizzi Pediatric Research Center “We discovered that individuals carrying the P2X7R mutation are predisposed to develop an altered immune response thanks to the opportunity we had to analyze an international cohort comprising more than 600 heart transplant patients enrolled between the United States and Italy.”

By analyzing the immunological characteristics of the T lymphocytes of patients carrying the mutation in vitro, the researchers verified a change in the immune response toward the development of damaging T lymphocytes, which in transplant patients is associated with the onset of numerous immunological events such as acute and chronic rejection that in the long term lead to the loss of the transplanted organ.

Dr. Francesca D”Addio asserts that understanding the malfunction of the mutated P2X7R receptor has allowed us to identify a group of individuals who might be affected by HyperTh17 syndrome,” says Dr. D’Addio, a researcher at the Department of Biomedical and Clinical Sciences “L. Sacco” of the State University of Milan and the Romeo and Enrica Invernizzi Pediatric Research Center of the University of Milan.

Further studies will be needed to determine the relevance of the P2X7 receptor mutation in diabetic and nontransplanted subjects to understand the association with the development of immunologic events.