Publication

The lectin pathway in renal disease: old concept and new insights

da Costa, M. G., Poppelaars, F., Berger, S. P., Daha, M. R. & Seelen, M. A., 1-Dec-2018, In : Nephrology Dialysis Transplantation. 33, 12, p. 2073-2079 7 p.

Research output: Contribution to journalReview articleAcademicpeer-review

Copy link to clipboard

Documents

  • The lectin pathway in renal disease: old concept and new insights

    Final publisher's version, 681 KB, PDF-document

DOI

The complement system is composed of a network of at least 40 proteins, which significantly contributes to health and disease. The lectin pathway (LP) is one of three pathways that can activate the complement system. Next to protection of the host against pathogens, the LP has been shown to play a crucial role in multiple renal diseases as well as during renal replacement therapy. Therefore, several complement-targeted drugs are currently being explored in clinical trials. Among these complement inhibitors, specific LP inhibitors are also being tested in renal abnormalities such as in immunoglobulin A nephropathy and lupus nephritis. Using various in vitro models, Yaseen et al. (Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement component 3 (C3) in absence of C4 and/or C2. FASEB J 2017; 31: 2210-2219) showed that Mannan-associated serine protease2 can directly activate C3 thereby bypassing C2 and C4 in the activation of the LP. These new findings broaden our understanding of the mechanisms of complement activation and could potentially impact our strategies to inhibit the LP in renal diseases. In support of these findings, we present data of human renal biopsies, demonstrating the occurrence of the LP bypass mechanism in vivo. In conclusion, this review provides a detailed overview of the LP and clarifies the recently described bypass mechanism and its relevance. Finally, we speculate on the role of the C4 bypass mechanism in other renal diseases.

Original languageEnglish
Pages (from-to)2073-2079
Number of pages7
JournalNephrology Dialysis Transplantation
Volume33
Issue number12
Publication statusPublished - 1-Dec-2018

    Keywords

  • complement, ischaemia reperfusion injury, kidney, lectin pathway, MASP-2, COMPLEMENT ACTIVATION, GLOMERULAR ACTIVATION, BINDING PROTEIN, ASSOCIATION, DEFECT, C4D, PATHOGENESIS, NEPHROPATHY, DEPOSITION, PATTERN

View graph of relations

ID: 76687532