Periodic Reporting for period 1 - StopAutoimmunity (Recurrent disease in the liver transplant: window to identify and stop gut signals driving autoimmunity)
Reporting period: 2019-04-01 to 2020-09-30
This hypothesis is investigated by using a an autoimmune disease of the bile ducts of the liver as a model system. The disease is called primary sclerosing cholangitis (PSC), and during the disease course, chronic inflammation of the bile ducts leads to scarring, accumulation of bile in the liver and ultimately liver failure. PSC is therefore one of the most common reasons for liver transplantation. After transplantation there is unfortunately a high risk of recurrent PSC (rPSC) although the patients receive special immunosuppressive therapy in order to tolerate their new liver. There is no medical treatment available that has been shown to slow or prevent the disease or disease progression in either PSC or rPSC. These conditions are therefore both challenging clinical and societal problems. In the context of research, however, the phenomenon of recurrent disease after a transplantation also represents an opportunity to study disease mechanisms in detail, because the patients are followed closely. This is what we like to call "the post transplant window". The mechanisms of autoimmunity, which we discover in PSC/rPSC, could be relevant also for other autoimmune diseases. Our projects may therefore serve both disease-specific and more general purposes.
The overall objectives of the study are to identify "gut signals" that are present in both PSC and rPSC (suggesting that the same signals are driving disease all the time). We will do this by investigating microbial genes in the intestine and microbial products in blood. In the next phase we will look for possible treatments to alter these "gut signals" and finally we will perform a pilot trial to test the potential of such a treatment to influence the disease. The outcome of StopAutoimmunity will be gut signals useful as novel biomarkers and treatment targets. These may directly translate into improved patient care but also provide a foundation for understanding the mechanisms of autoimmunity.
We have also performed a large scale analysis of >1000 different biochemical substances in blood, some of which are of bacterial origin. This is a very important discovery tool and we already have interesting observations that we follow up on.