Autoimmune diseases

Whereas our immune system normally guards us against pathogens such as bacteria andviruses, it can mistakenly attack our own body and thereby cause severe health problems. These abnormal immune responses are collectively described as autoimmunity, a condition of which more than 80 different subtypes are identified. Well known examples are type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus. Some autoimmune diseases run in families, whereas others seem to be triggered by environmental factors. Some types affect a single organ or cell type, while another type affects the whole body. Due to this diversity and complexity finding the right diagnosis and treatment can be enormously difficult.

Within this program at AbSano we aim to develop monoclonal antibodies which will aid patients and healthcare professionals to diagnose and treat autoimmunity. Monoclonal antibodies can be valuable tools to visualize the location of inflammation or be used as a therapy by blocking overactive immune system components such as pro-inflammatory cytokines. At AbSano we have selected targets with a role in autoimmune diseases, for which specific antibodies would provide valuable diagnostic or therapeutic tools. As part of one of these subprograms we develop antibodies against collagen, which we believe to be of great benefit in the area of rheumatic diseases.

Rheumatic diseases, such as rheumatoid arthritis (RA), start with initial erosion of the cartilage layer within the joint. Subsequently, the underlying bone structure is affected, which can severely disturb joint function and lead to disability. Starting effective therapy within the first two years of clinical symptoms has been shown to result in a better long-term disease outcome (19). Still, 30-50% of all RA patients do not respond to any of the available treatment options (20). Due to the heterogeneous nature of the diseases themselves and high patient variation in response to treatment, rheumatic diseases require individualized treatment strategies. Current imaging strategies focus on the presence of synovial inflammation (21). However, the inflammatory response is heterogeneous and not always directly related to disease outcome. Destruction of the cartilage affects joint function and is, in addition to synovial inflammation, affected by immunological and mechanical triggers as well as the type of immune cells involved. As cartilage erosion is directly affecting disease outcome, measuring the level of cartilage destruction would be a more suitable target for novel imaging strategies.

Intact cartilage consists of a network of collagen type II, which is protected by proteoglycans and thereby not available for binding receptor molecules (22). During early stages of rheumatic diseases, metalloproteinases expose the collagen fibers by degrading the proteoglycans. Subsequent breakdown of the collagen is essentially irreversible and a key step in the destruction of connective tissue. A non-invasive and quantitative method to measure the level of exposed collagen type II would enable direct monitoring of the level of cartilage damage.

Together with the group of Dr. Peter van Lent at the Radboud University Medical Center, we are developing and validating antibodies specifically recognizing collagen type II. The optimized product will allow us to visualize and quantify the presence of damaged cartilage in rheumatic diseases. We believe that these antibodies will greatly benefit patients and healthcare. Improving our ability to monitor treatment effects will increase the chances of finding an effective therapy within the first two years of symptoms and thereby result in a better disease outcome. Additionally, it would enable us to treat patients based on their rate of cartilage destruction and thereby provide a great opportunity for personalized medicine.

19. Kyburz D, Finckh A. Physicians of SCQM-RA. The long-term impact of early treatment of rheumatoid arthritis on radiographic progression: a population-based cohort study. Rheumatology 2011, 50:1106-10

20. Astorri E, Pitzalis C. Towards a stratified targeted approach with biologic treatments in rheumatoid arthritis: role of synovial pathobiology. Curr Pharm Des 2015, 21:2216-24

21. Wang Y, Cicuttini FM. Osteoarthritis year in review 2015: imaging. Osteoarthritis Cartilage 2016, 24:49-57

22. Eyre D. Collagen of articular cartilage. Arthritis Res 2002, 4:30-5