title: "Kill" the messenger: Targeting of cell-derived microparticles in lupus nephritis.
abstract: Immune complex (IC) deposition in the glomerular basement membrane (GBM) is a key early pathogenic event in lupus nephritis (LN). The clarification of the mechanisms behind IC deposition will enable targeted therapy in the future. Circulating cell-derived microparticles (MPs) have been proposed as major sources of extracellular autoantigens and ICs and triggers of autoimmunity in LN. The overabundance of galectin-3-binding protein (G3BP) along with immunoglobulins and a few other proteins specifically distinguish circulating MPs in patients with systemic lupus erythematosus (SLE), and this is most pronounced in patients with active LN. G3BP co-localizes with deposited ICs in renal biopsies from LN patients supporting a significant presence of MPs in the IC deposits. G3BP binds strongly to glomerular basement membrane proteins and integrins. Accordingly, MP surface proteins, especially G3BP, may be essential for the deposition of ICs in kidneys and thus for the ensuing formation of MP-derived electron dense structures in the GBM, and immune activation in LN. This review focuses on the notion of targeting surface molecules on MPs as an entirely novel treatment strategy in LN. By targeting MPs, a double hit may be achieved by attenuating both the autoantigenic fueling of immune complexes and the triggering of the adaptive immune system. Thereby, early pathogenic events may be blocked in contrast to current treatment strategies that primarily target and modulate later events in the cellular and humoral immune response.
authors.affiliation: Copenhagen Lupus and Vasculitis Clinic, Centre for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Christoffer T
authors.initials: CT
authors.lastname: Nielsen
authors.affiliation: Copenhagen Lupus and Vasculitis Clinic, Centre for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Niclas S
authors.initials: NS
authors.lastname: Rasmussen
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
authors.affiliation: Copenhagen Lupus and Vasculitis Clinic, Centre for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Denmark. Electronic address: soeren.jacobsen.01@regionh.dk.
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology*; D017209:Apoptosis; D055252:Cell-Derived Microparticles / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex
keywords: Apoptosis; Electron dense deposits; Galectin-3-binding protein; Immune complexes; Lupus nephritis; Microparticles