Asparaginase inhibits the lectin pathway of complement activation

Mol Immunol. 2018 Jan:93:189-192. doi: 10.1016/j.molimm.2017.11.027. Epub 2017 Dec 1.

Abstract

Oncological treatment has been associated with an increased risk of infection, most often related to therapy-induced pancytopenia. However, limited research has been conducted on the effect of oncological therapy on the complement system, being part of the non-cellular innate immune system. This became the rationale for an observational clinical study (C2012) in which we have investigated the prevalence of transient complement defects. Once we had observed such defects, a correlation of the complement defects to specific clinical parameters or to specific therapeutic regimens was investigated. A prominent defect observed in C2012 was the inhibition of the lectin pathway (LP) of complement activation during the treatment of acute lymphoblastic leukemia (ALL), which we could directly associate to the use of asparaginase (ASNase). Ex-vivo experiments confirmed a direct dose-dependent inhibitory effect of ASNase on the LP functionality.

Keywords: Asparaginase; Complement activation; Lectin pathway; Oncology; Selective inhibiton.

Publication types

  • Observational Study

MeSH terms

  • Asparaginase / administration & dosage
  • Asparaginase / pharmacology*
  • Asparaginase / therapeutic use
  • Child
  • Complement Pathway, Mannose-Binding Lectin / drug effects*
  • Depression, Chemical
  • Dose-Response Relationship, Drug
  • Humans
  • Mannose-Binding Lectin / blood
  • Mannose-Binding Protein-Associated Serine Proteases / antagonists & inhibitors
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / pharmacology*
  • Polyethylene Glycols / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Protein Binding / drug effects

Substances

  • Mannose-Binding Lectin
  • Polyethylene Glycols
  • pegaspargase
  • Mannose-Binding Protein-Associated Serine Proteases
  • Asparaginase