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 -