Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.
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.
['Nielsen|C T|CT|', 'Østergaard|O|O|', 'Rekvig|O P|OP|', 'Sturfelt|G|G|', 'Jacobsen|S|S|', 'Heegaard|N H H|NH|']
D000328:Adult D000368:Aged D000936:Antigen-Antibody Complex D000951:Antigens, Neoplasm D014408:Biomarkers, Tumor D001798:Blood Proteins D002352:Carrier Proteins D016022:Case-Control Studies D055252:Cell-Derived Microparticles D015922:Complement C1q D003430:Cross-Sectional Studies D005260:Female D005434:Flow Cytometry D037502:Galectin 3 D037161:Galectins D015432:Glomerulonephritis, Membranoproliferative D006023:Glycoproteins D006801:Humans D007074:Immunoglobulin G D007674:Kidney Diseases D007678:Kidney Glomerulus D008181:Lupus Nephritis D008297:Male D008562:Membrane Glycoproteins D008875:Middle Aged D053719:Tandem Mass Spectrometry D055815:Young Adult
microparticles lupus nephritis Galectin-3-binding protein systemic lupus erythematosus immune complexes Mac-2-binding protein electron dense deposits