Leiden University Scholarly Publications

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Essen, M.F. van (2022)

Multifaceted role of the complement system in health and disease: a focus on properdin

Doctoral Thesis
Transplantation is the golden standard for the treatment of end-stage renal disease. During this process, the transplanted organ is often damaged. In this thesis, we investigated whether activation of the complement system, part of our innate immune system, plays a local role. We reviewed that properdin, the only known positive regulator of the complement system, was detected in serum, plasma and urine from patients with various complement-mediated renal diseases. In protocol biopsies obtained 10 days after transplantation, properdin was found deposited in addition to complement activation markers. Next, we showed that dendritic cells secrete properdin and a decrease in properdin levels during dendritic cell- T-cell interaction resulted in reduced T-cell proliferation and activation. We also showed that properdin is able to bind to surfaces of both viable and dead cells, contributing to complement activation. Macrophages can also produce properdin and negative regulators factor H...Show moreTransplantation is the golden standard for the treatment of end-stage renal disease. During this process, the transplanted organ is often damaged. In this thesis, we investigated whether activation of the complement system, part of our innate immune system, plays a local role. We reviewed that properdin, the only known positive regulator of the complement system, was detected in serum, plasma and urine from patients with various complement-mediated renal diseases. In protocol biopsies obtained 10 days after transplantation, properdin was found deposited in addition to complement activation markers. Next, we showed that dendritic cells secrete properdin and a decrease in properdin levels during dendritic cell- T-cell interaction resulted in reduced T-cell proliferation and activation. We also showed that properdin is able to bind to surfaces of both viable and dead cells, contributing to complement activation. Macrophages can also produce properdin and negative regulators factor H and its splice variant FHL-1. Increasing knowledge on complement factor production by other cells than hepatocytes, including immune cells, hints towards a local role of the complement system in various processes. These findings contribute to a better understanding of the local role of the complement system and are important for the applications of (new) complement-inhibiting drugs.
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Complement system
Dendritic cells
Factor H
Macrophages
Properdin
T cells
Transplantation
All authors
Essen, M.F. van
Supervisor
Kooten, C. van
Co-supervisor
Ruben, J.M.
Committee
Rabelink, A.J.; Trouw, L.A.; Kar, N.C.A.J. van de; Berger, S.P.
Qualification
Doctor (dr.)
Awarding Institution
LUMC - Medische Faculteit Leiden, Leiden University
Date
2022-10-06
ISBN (print)
9789464583625

Funding

Sponsorship
The research described in this thesis was performed with financial support from the Dutch Kidney Foundation (COMBAT consortium grant 13OCA27). The printing of this thesis was financially supported by Hycult Biotech.