title: Factor H inhibits complement activation induced by liposomal and micellar drugs and the therapeutic antibody rituximab in vitro.
abstract: Hypersensitivity reactions to particulate drugs can partly be caused by complement activation and represent a major complication during intravenous application of nanomedicines. Several liposomal and micellar drugs and carriers, and therapeutic antibodies, were shown to activate complement and induce complement activation-related pseudoallergy (CARPA) in model animals. To explore the possible use of the natural complement inhibitor factor H (FH) against CARPA, we examined the effect of FH on complement activation induced by CARPAgenic drugs. Exogenous FH inhibited complement activation induced by the antifungal liposomal Amphotericin-B (AmBisome), the widely used solvent of anticancer drugs Cremophor EL, and the anticancer monoclonal antibody rituximab in vitro. An engineered form of FH (mini-FH) was more potent inhibitor of Ambisome-, Cremophor EL- and rituximab-induced complement activation than FH. The FH-related protein CFHR1 had no inhibitory effect. Our data suggest that FH or its derivatives may be considered in the pharmacological prevention of CARPA.
  
  
  BACKGROUND
  Although liposomes and micelles are already in use in the clinical setting as drug carriers, there remains the potential problem of hypersensitivity due to complement activation. In this article, the authors investigated the use of complement inhibitor factor H (FH) on complement activation and showed good efficacy. The results would therefore suggest the potential application of complement inhibitor in the future.
authors.affiliation: Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary; SeroScience Ltd., Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Mészáros
authors.affiliation: MTA-ELTE "Lendület" Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Ádám I
authors.initials: ÁI
authors.lastname: Csincsi
authors.affiliation: MTA-ELTE Immunology Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Barbara
authors.initials: B
authors.lastname: Uzonyi
authors.affiliation: Junior Research Group for Cellular Immunobiology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Hebecker
authors.affiliation: Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary; SeroScience Ltd., Budapest, Hungary.
authors.forename: Tamás G
authors.initials: TG
authors.lastname: Fülöp
authors.affiliation: MTA-ELTE Immunology Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary; Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Erdei
authors.affiliation: Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary; SeroScience Ltd., Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Szebeni
authors.affiliation: MTA-ELTE "Lendület" Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary. Electronic address: mihaly.jozsi@gmx.net.
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
mesh_terms: D003167:Complement Activation / Q000187:drug effects* / Q000276:immunology; D017242:Complement Factor H / Q000008:administration & dosage* / Q000276:immunology; D004337:Drug Carriers / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D064368:Healthy Volunteers; D006801:Humans; D008081:Liposomes / Q000009:adverse effects*; D008823:Micelles; D050997:Nanomedicine; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D000069283:Rituximab / Q000009:adverse effects
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D008823:Micelles; D000069283:Rituximab; D017242:Complement Factor H
keywords: Complement; Factor H; Hypersensitivity; Nanomedicine; Pseudoallergy