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Reduction of complement factor H binding to CLL cells improves the induction of rituximab-mediated complement-dependent cytotoxicity.
- Source :
-
Leukemia (08876924) . Nov2013, Vol. 27 Issue 11, p2200-2208. 9p. - Publication Year :
- 2013
-
Abstract
- A main effector mechanism of rituximab (RTX) is the induction of complement-dependent cytotoxicity (CDC). However, this effector function is limited, because CLL cells are protected from complement-induced damage by regulators of complement activation (RCAs). A prominent RCA in fluid phase is factor H (fH), which has not been investigated in this context yet. Here, we show that fH binds to CLL cells and that human recombinant fH-derived short-consensus repeat 18-20 (hSCR18-20) interferes with this binding. In complement-based lysis assays, CLL cells from therapy-naive patients were differently susceptible to RTX-induced CDC and were defined as CDC responder or CDC non-responder, respectively. In CDC responders, but notably also in non-responders, hSCR18-20 significantly boosted RTX-induced CDC. Killing of the cells was specific for CD20+ cells, whereas CD20− cells were poorly affected. CDC resistance was independent of expression of the membrane-anchored RCAs CD55 and CD59, although blocking of these RCAs further boosted CDC. Thus, inhibition of fH binding by hSCR18-20 sensitizes CLL cells to CDC and may provide a novel strategy for improving RTX-containing immunochemotherapy of CLL patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 27
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 91819007
- Full Text :
- https://doi.org/10.1038/leu.2013.169