Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis

TY - JOUR

T1 - Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis

AU - Nielsen, C T

AU - Østergaard, O

AU - Rekvig, O P

AU - Sturfelt, G

AU - Jacobsen, S

AU - Heegaard, N H H

N1 - © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

PY - 2015/10/11

Y1 - 2015/10/11

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Antigen-Antibody Complex/blood

KW - Antigens, Neoplasm/blood

KW - Biomarkers, Tumor/blood

KW - Carrier Proteins/blood

KW - Case-Control Studies

KW - Cell-Derived Microparticles/metabolism

KW - Complement C1q/immunology

KW - Cross-Sectional Studies

KW - Female

KW - Flow Cytometry/methods

KW - Galectin 3/metabolism

KW - Glomerulonephritis, Membranoproliferative/metabolism

KW - Glycoproteins/blood

KW - Humans

KW - Immunoglobulin G/blood

KW - Kidney Diseases/pathology

KW - Kidney Glomerulus/pathology

KW - Lupus Nephritis/blood

KW - Male

KW - Membrane Glycoproteins/metabolism

KW - Middle Aged

KW - Tandem Mass Spectrometry/methods

KW - Young Adult

U2 - 10.1177/0961203315580146

DO - 10.1177/0961203315580146

M3 - Journal article

C2 - 25837289

SN - 0961-2033

VL - 24

SP - 1150

EP - 1160

JO - Lupus

JF - Lupus

IS - 11

ER -