Scientists from the Leibniz Institute for Natural Product Research and Infection Biology / Hans Knöll Institute in Jena, Germany, have identified a human protein that triggers autoinflammatory reactions. If the inflammation is part of the healing process, it worsens the situation in patients with chronic vasculitis, for example.
Long-lasting inflammations are a side effect of many diseases. Especially in the case of infections with bacteria, fungi or viruses, they serve to slow down the multiplication of the pathogens by increasing temperature and by activating the immune system components that support the healing process. In chronic autoinflammatory diseases, however, the inflammatory reaction does not enter the healing process. The body's own cells lose their balance and the disease process is intensified. The course of the disease is often chronic or intermittent.
A research team led by Jena scientists has now identified a protein that is responsible for autoinflammatory reactions in humans. The body's own factor H-related protein (CFHR) FHR1 binds to dying cells that develop in various human diseases. It thus triggers an inflammatory reaction that intensifies the disease and can severely affect the patient's wellbeing. Common diseases, as well as rare diseases such as ANCA-associated vasculitis (AAV), are affected.
"In our study, we were able to show that FHR1 molecules specifically bind to dying cells in the blood vessels, whereas closely related proteins such as Factor H or FHR2 and FHR3 do not," said Christine Skerka, lead investigator of the study. The Professor of Immunoregulation at the Jena-based Hans Knöll Institute heads a research group dealing with the complex interaction of molecules of the immune system in infectious and non-infectious diseases.
"The binding of FHR1 to the cell surface triggers the activation of the immune protein NLRP 3 (the inflammasome) in the body, which eventually triggers an entire inflammatory chain that leads to autoinflammation," continued Skerka. The results of the study coincide with the observation that a deficiency of FHR1 protects against certain diseases. The protein FHR1 could, therefore, be a promising target for drugs to reduce inflammatory reactions in the body. Antibodies that inhibit FHR1 have already been successfully tested in vitro.
Irmscher S, Brix SR, Zipfel SLH, Halder LD, Mutlutürk S, Wulf S, Girdauskas E, Reichenspurner H, Stahl RAK, Jungnickel B, Wiech T, Zipfel PF, Skerka C (2019) Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathy. Nat Commun 10, 2961. doi: 10.1038/s41467-019-10766-0.