Cum laude Thesis defense Richard Pouw: Complement Factor H and its related proteins

Richard Pouw

On 27 November 2018 Richard Pouw defended his thesis at the University of Amsterdam. Due to the excellent quality of the research presented in his thesis and the defense Richard received his doctorate cum laude. 

Richard investigated the balance between complement regulator factor H (FH) and the FH-related proteins (FHRs) in meningococcal disease and atypical hemolytic uremic syndrome (aHUS). His research provides new tools and leads to further investigations of FHRs in various diseases. In addition, it has led to the discovery of a new method to improve FH function with therapeutic potential.

Complement is a crucial part of innate immunity and consists of proteins that circulate in blood and protect the body against pathogens that enter the bloodstream. In order to quickly detect and kill pathogens, complement is continuously active, causing it to ‘attack’ all cells it encounters. Under healthy conditions, human cells are protected against complement by regulators such as complement factor H (FH). If FH function is decreased, diseases like aHUS can occur. Furthermore, to escape complement-mediated clearance, pathogens hijack FH.

Risk factors

Humans also possess FHRs, which are thought to in turn regulate FH function. It is unknown how FHRs affect diseases like aHUS or the hijacking of FH by pathogens. In this thesis Richard Pouw focusses on FH and the FHRs during health, meningococcal disease (MD) and aHUS. The research led to the first determination of FHR levels in blood showing that during health, FH is 60-fold more abundant than FHR-3 and FHR-4A. FH and not FHR-3 was found to be a risk factor for MD, while increased FHR-3 levels were found in aHUS patients. The research has shown that FHR-3 plays a smaller role in MD than originally hypothesized. It also provides new tools and leads to further investigate FHR proteins in various diseases.

Therapeutic potential

In addition, the research has led to the discovery of a new method to improve FH function, which has therapeutic potential in diseases in which FH function is decreased. This is currently being further developed by Sanquin, in collaboration with Gemini Therapeutics.

Thesis: Setting the scale: The balance between complement factor H and its related proteins in health and disease

Promotor: Prof  TW Kuijpers MD PhD
Co-promotor: D Wouters PhD

Venue: University of Amsterdam, Agnietenkapel