Asparaginase inhibits the lectin pathway of complement activation. (January 2018)

• Record Type: Journal Article
• Authors: Keizer, M.P.; Aarts, C.; Kamp, A.M.; Caron, H.N.; van de Wetering, M.D.; Wouters, D.; Kuijpers, T.W.
• Is Part Of: Molecular immunology. Volume 93(2018:Jan.)
• Page Start: 189
• Page End: 192
• Publication Date: 2018-01
• Subjects: Complement activation -- Lectin pathway -- Selective inhibiton -- Asparaginase -- Oncology; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2017.11.027
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Asparaginase inhibits the lectin pathway of complement activation. Inhibition by Asparaginase is independent of liver protein synthesis. Therapy-induced inhibition of the complement system could be a risk factor for infection. 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.