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

Mariana Gaya da Costa1, Felix Poppelaars1, Stefan P Berger1

  • 1Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|April 28, 2018
PubMed

Insights

The lectin pathway (LP) can activate complement component 3 (C3) bypassing C2 and C4. This bypass mechanism, observed in vitro and in vivo, offers new insights into renal diseases and complement inhibition strategies.

Area of Science:

  • Immunology
  • Nephrology
  • Biochemistry

Background:

  • The complement system, a key part of innate immunity, involves over 40 proteins contributing to health and disease.
  • The lectin pathway (LP) is one of three complement activation pathways, crucial for pathogen defense and implicated in renal diseases.
  • Current research focuses on complement inhibitors, including specific LP inhibitors, for treating renal abnormalities like IgA nephropathy and lupus nephritis.

Purpose of the Study:

  • To review the lectin pathway (LP) of complement activation.
  • To clarify a recently described LP bypass mechanism involving mannan-binding lectin-associated serine protease-2 (MASP-2).
  • To discuss the relevance of this bypass mechanism in renal diseases and complement-targeted therapies.

Main Methods:

  • Review of existing literature on the complement system and lectin pathway.
  • Analysis of in vitro studies demonstrating MASP-2's ability to activate C3 directly.
  • Presentation of in vivo data from human renal biopsies supporting the LP bypass mechanism.

Main Results:

  • Mannan-binding lectin-associated serine protease-2 (MASP-2) can directly activate complement component 3 (C3).
  • This activation bypasses the need for C2 and C4 in the lectin pathway.
  • The LP bypass mechanism was confirmed in human renal biopsies, indicating its in vivo relevance.

Conclusions:

  • The discovery of the LP bypass mechanism broadens the understanding of complement activation.
  • This bypass mechanism has potential implications for developing targeted therapies for renal diseases.
  • Further investigation into the C4 bypass mechanism's role in various renal conditions is warranted.

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