Researchers at Linköping University in Sweden have discovered that C-reactive protein (CRP), a common biomarker that is routinely used to detect systemic inflammation, plays a beneficial role in systemic lupus erythematosus (SLE), the most common form of lupus. The research, published in the Journal of Autoimmunity, opens a new avenue for the potential use of CRP for this form of the autoimmune disorder.
Study leader Christopher Sjöwall, MD, PhD, senior associate professor in the department of biomedical and clinical sciences, BKV, at Linköping University has spent a number of years studying SLE to better understand the root causes of this autoimmune disease. He noted that when inflammatory activity is high in SLE, people show a lower level of CRP than would be expected. Prior animal studies with lupus-prone disease showed milder disease symptoms and lower antibody levels when given CRP. This suggests the protein would also have a beneficial effect in humans.
“CRP is an ancient protein and similar proteins can be found in all animals, even in primitive organisms. When a protein has been so well preserved throughout evolution, this usually means that it has an important function. CRP is used a lot in clinical care as a marker of ongoing inflammation, but few have studied its biological effects,” said Sjöwall.
For their study, the Linköping University team examined the impact of interferon and other signaling proteins caused by CRP alone with immune complexes specific to SLE that are formed by antibodies that have reacted to material from dead cells. One component of the research was to discover what happens when serum samples collected from 15 SLE patients with varying levels of CRP were added to healthy cells. Their findings indicated that when CRP levels were low there were higher levels of interferon than when CRP levels were high indicating that CRP helped reduce interferon response.
Interestingly, the team found that the shape of CRP is also important. CRP consists of five identical units (pentamer shape), each of which can split and function independently (monomer shape), referred to as pCRP and mCRP respectively. In their study, the investigators showed only pCRP reduced the activity of interferon.
“The finding that the pentamer shape of CRP can suppress the immune response is interesting also in the context of other diseases, such as various virus diseases,” said Marie Larsson, PhD, professor of virology in BKV at Linköping University and one of the contributing researchers to the study.
Based on this new finding, the investigators believe they have uncovered a new avenue for research into developing therapeutics that can reduce immune complexes and elevated interferon levels for the treatment of autoimmune diseases. They warn, however, that since interferon plays an important role in beneficial immune response to ward off infections, finding the right balance of treatments for SLE and similar diseases will require continued research.
