In addition to the clinical research, the LuVaCs center of expertise also hosts a fundamental immunology research team. Professor Cees van Kooten is the head of our nephro-immunology lab and is supported by our research technicians, PhD students and postdocs. This unique combination of clinical practice and the availability of fundamental knowledge on immunology of the diseases, allows us to connect results from lab-experiments to clinical patient data. In order to do this, we also have a large LuVaCs biobank with patient data and material. Our complement-related research is in close collaboration with the research group of Professor Leendert Trouw of the Department of Immunology of the LUMC. In addition, for our B-cell research we have strong connections with the research group of dr. Jolien Suurmond and prof. Diane van der Woude of the Department of Rheumatology.
On this page, you find more information about our 4 research themes and the corresponding projects in the scope of the themes.
Theme 1: (local) Complement activation and inhibition
In the lab, we study the (local) activation and regulation of the complement system, a key component of the innate immune system. Patients at the LuVaCs (outpatient) clinic often have an overactive complement system, contributing to disease onset and progression. Gaining a better understanding of the functions and interactions of the complement system in these patients is therefore essential. Our research is focused on several aspects related to the role of complement in systemic autoimmune diseases: (1) where does complement activation occur, (2) why is the complement system overactivated, with a focus on positive regulator properdin and factor B, (3) what are the effects of complement activation both locally (in the kidney) and systemically (in the blood circulation), and (4) do complement inhibitors also have local inhibitory effects, and if so, how does that work. In recent years, the panel of complement inhibitory drugs has become increasingly diverse and sophisticated, offering therapeutic options for a range of complement-mediated diseases, including several systemic autoimmune diseases. An example is avacopan, which was shown to be highly effective in a large clinical trial for the treatment of ANCA-associated vasculitis.
Theme 2: B cells & antibodies
Bcells are part of the adaptive immune system and are capable of producing antibodies. When B cells produce antibodies that recognize the body’s own proteins, we refer to them as autoantibodies, which can be detected in the blood. In patients with ANCA-associated vasculitis, for example, we can detect autoantibodies directed against PR3 and MPO, proteins produced by neutrophils. In SLE, we observe autoantibodies targeting components of the cell nucleus, including NETs. Our lab studies B cells using high sensitivity flow cytometry, to help us detect indications of disease activity at an early stage. This could contribute to timely treatment of the patient, potentially enabling us to suppress or even prevent disease flares.
Breaking ANCA
This study-project is collaboration between the LUMC and Stanford University (USA). This project explores how breaks in the nasal lining might trigger autoimmune responses in ANCA-associated vasculitis (AAV), aiming to uncover new treatment possibilities. This collaboration was enabled by the Marie Curie Fellowship Grant. Read more information here: https://lauravandam.com/breaking-anca-marie-curie-fellowship/
Theme 3: Neutrophil extracullular traps (NETs)
Among the key cellular components involved in systemic autoimmune diseases are neutrophils. Neutrophils are a type of granulocyte and are part of our innate immune system. They are one of the first leukocytes to infiltrate sites of infection and inflammation. A unique property of activated neutrophils is their ability to “spit out” a web of DNA and proteins, so-called neutrophil extracellular traps (NETs). These NETs function as traps to capture invading pathogens, aiding in their clearance and preventing their dissemination from the site of infection. NETs can, however, also contribute to tissue damage and inflammation when not properly regulated. Increased production and/or decreased degradation of NETs allows access to a source of autoantigens that are embedded in NETs, thereby contributing to (and potentially driving) autoimmunity. Indeed, persistent NETs are implicated in, for example, SLE. In the lab, we are investigating the triggers that lead to the formation of NETs and examining whether there are differences among patients in their ability to degrade NETs. We correlate these fundamental findings with the clinical data of our patient cohort.
Theme 4: Digital health & Real-world Evidence (RWE)
In our center of expertise, we also pay attention to implementing digital healthcare and utilizing real-world data. We developed digital health care pathways for AAV and SLE, implemented these as standard of care at our outpatient clinics and we are continuously monitoring and improving the pathways. We aim to determine how digital monitoring, smart notifications and AI-based predictions can help improve care to reduce patient burdens and healthcare utilization.
Additionally, we use AI-based tools to accurately identify AAV, SLE and C3G patients to be able to easily collect and analyze data which help us create new insights that can help innovate treatment and improve quality of care.
THiNK project
THiNK is an observational study aiming to evaluate the impact of implementing digital care pathways for AAV and SLE patients on healthcare outcomes, healthcare utilization, and healthcare costs. The study is conducted from 2022 to 2030, and is not supported by a subsidy.
VIDIVAS project
VIDIVAS is an observational study aiming to integrate risk-assessments for relapses and infections within the digital care pathways of AAV and determine value-based impact on patients’ burdens and hospital costs. The study will be conducted from 2025 to 2028, and is subsidised by the private-public-cooperation grant (PPS) of Health Holland, together with DEARhealth.