Galectin-3-Binding Protein Is Highly Increased On Circulating Microparticles In SLE Patients and Co-Localizes With IgG In Glomerular Deposits In Human Lupus Nephritis

Christoffer T. Nielsen^1,2, Ole Østergaard³, Ole Petter Rekvig⁴, Gunnar K. Sturfelt⁵, Søren Jacobsen⁶ and Niels H. H. Heegaard⁷, ¹Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen S, Denmark, ²Infectious Diseases and Rheumatology, University Hospital Rigshospitalet, Copenhagen, Denmark, ³Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institute, Copenhagen S, Denmark, ⁴Department of Biochemistry and Medical Biology, University Hospital, Tromsø, Norway, ⁵Department of Rheumatology, University Hospital Lund, Lund, Sweden, ⁶Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, ⁷Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: autoantigens, galectin, lupus nephritis and microparticles, SLE

Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Mechanisms and Biomarkers

Session Type: Abstract Submissions (ACR)

Background/Purpose: The origin of autoantigens in glomerular immune complex (IC) deposits in lupus nephritis patients is unknown. They may derive from the circulation (microparticle (MP)-ICs or soluble ICs) or from apoptotic glomerular cells. Galectin-3-binding protein (G3BP) may be a specific marker of SLE cell-derived MPs. Here, we characterize G3BP-positive MPs in plasma from SLE patients compared to healthy controls (HCs), explore clinical correlates, and use G3BP to identify MP-components in IC deposits in kidney biopsies from patients with lupus nephritis.

Methods: Plasma MPs were analyzed in 56 SLE patients and 36 healthy controls. MPs were enumerated by flow cytometry for G3BP exposure and annexin V (AnxV) binding. MP-quantitation of G3BP, IgG, and C1q were obtained by tandem mass spectrometry (LC-MS/MS). Co-localization of anti-G3BP antibodies with in vivo-bound IgG was examined in kidney biopsies from SLE patients with class IV (diffuse proliferative, n=2) and class IV (membranous, n=1) and in one control using co-localization immune electron microscopy.

Results: LC-MS/MS quantities of MP-G3BP, -IgG and -C1q were significantly increased in SLE patients (p<0.05 in all cases). Three different G3BP-positive MP-populations could be identified by flow cytometry. Two of these were significantly increased in SLE patients compared to HCs (p=0.008 and p=0.001, respectively). No significant clinical associations were observed. G3BP co-localized with in vivo-bound IgG in all three lupus nephritis biopsies while absent from control tissue. The G3BP was confined to the IC deposits and detected diffusely throughout the sections.

Conclusion: G3BP overexpression is a key feature of SLE-MPs irrespective of clinical manifestations or disease activity. The distinct overlap of glomerular G3BP and IC deposits strongly suggests MPs to be an important source of autoantigens in lupus nephritis.

Disclosure:

C. T. Nielsen,
None;

O. Østergaard,
None;

O. P. Rekvig,
None;

G. K. Sturfelt,
None;

S. Jacobsen,
None;

N. H. H. Heegaard,
None.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/galectin-3-binding-protein-is-highly-increased-on-circulating-microparticles-in-sle-patients-and-co-localizes-with-igg-in-glomerular-deposits-in-human-lupus-nephritis/