title: Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.
abstract: OBJECTIVE
  A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis.
  
  
  METHODS
  Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy.
  
  
  RESULTS
  Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P < 0.01) increased in SLE patients by LC-MS/MS. Three G3BP-exposing microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies.
  
  
  CONCLUSIONS
  Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major autoantigen source and provides a new understanding of the origin of immune complexes occurring in lupus nephritis.
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark Department of Infectious Disease and Rheumatology, University Hospital Rigshospitalet, Copenhagen, Denmark christoffertandrupnielsen@gmail.com.
authors.forename: C T
authors.initials: CT
authors.lastname: Nielsen
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Østergaard
authors.affiliation: RNA and Molecular Pathology Research Group, University of Tromsø, Tromsø, Norway.
authors.forename: O P
authors.initials: OP
authors.lastname: Rekvig
authors.affiliation: Department of Rheumatology, University Hospital of Lund, Lund, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Sturfelt
authors.affiliation: Department of Infectious Disease and Rheumatology, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Jacobsen
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: N H H
authors.initials: NH
authors.lastname: Heegaard
mesh_terms: D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000097:blood; D000951:Antigens, Neoplasm / Q000097:blood* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000473:pathology; D015922:Complement C1q / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D037502:Galectin 3 / Q000378:metabolism; D037161:Galectins; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007674:Kidney Diseases / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology*; D008181:Lupus Nephritis / Q000097:blood* / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult; D016326:Extracellular Matrix Proteins
chemical_list: D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001798:Blood Proteins; D002352:Carrier Proteins; D015922:Complement C1q; D037502:Galectin 3; D037161:Galectins; D006023:Glycoproteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C428445:LGALS3 protein, human; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins; C114782:TAA90K protein, human
keywords: Galectin-3-binding protein; Mac-2-binding protein; electron dense deposits; immune complexes; lupus nephritis; microparticles; systemic lupus erythematosus