Date: Monday, November 9, 2015
Session Title: Systemic Lupus Erythematosus - Animal Models Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: DNA, nucleosomes, and other deoxyribonucleoproteins (DNP) are currently believed to be the key autoantigens in SLE. However, these extracellular DNP itself appear to be just a cellular debris without any essential function. This paradox could open up a potential for degradation of the autoantigen and anti-dsDNA-containing ICs. We were to evaluate efficacy and safety of experimental in vivo blood perfusion through DNase I-containing magnetic beads under preliminary short-term examination using rat model of SLE-like alterations of DNP elimination.
Methods: In the experiments we used 20 female Wistar rats (50-54 weeks), randomized in 2 groups. Precalculated group size was 10 rats for each group. All the experimental protocols fulfilled the Declaration of Helsinki of the World Medical Association. The SLE-like disorders of DNP elimination were simulated by method of N. Jiang et al (2003) which was followed by intravenous injection of anti-dsDNA. Magnetic beads were synthesized using the emulsion polymerization technique. In the experimental group after preliminary heparinization blood was perfused through mini column with DNase I-containing magnetic beads (0.2 ml). Beads for the placebo group didn’t contain any active substance. Titers of IgG deposited in rat kidneys (IgGf) were measured by direct immunofluorescence on kidney cryoslices, serum circulating immune complexes (CIC) by polyethylene glycol precipitation assay, and plasma DNA by fluorimetry with PicoGreen. serum anti-dsDNA, CBC, total plasma protein, plasma creatinine, ALT, and AST were determined using conventional methods. All these measurements except IgGfwere performed before and after perfusion.
Results: There were no significant differences between experimental and placebo groups in the initial marker means. We revealed distinct differences between the experimental and placebo control groups in DNA (p<0.001) and CIC concentrations (p<0.001) after the perfusion. Geometric mean of IgGftiter was significantly higher in placebo perfusion group comparing to perfusion through DNase I-containing beads (p=0.002). After the perfusion serum creatinine, being initially increased, demonstrated significant lowering in the experimental group comparing to placebo (p<0.001). Other markers didn’t reveal any significant changes in both groups.
Conclusion: We have demonstrated clear efficacy of the extracorporeal perfusion in vivo for preventing kidney damage by diminishing of circulating DNA and CIC. As we speculated, the modeling protocol simulates not only glomerular deposition of DNA-containing immune complexes, but also induced filtration disorder. Lowering of DNA and DNA-containing immune complexes by the perfusion could diminish the extent of kidney damage. There was no blood cell destruction or hepatotoxicity during our experiment.
To cite this abstract in AMA style:Simakova E, Trofimenko A, Gontar I, Zborovskaya I. A New Perspective in Extracorporeal Immunotherapy of Systemic Lupus Erythematosus: Dnase I-Based Blood Perfusion Experiment Using Rat Model [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/a-new-perspective-in-extracorporeal-immunotherapy-of-systemic-lupus-erythematosus-dnase-i-based-blood-perfusion-experiment-using-rat-model/. Accessed May 26, 2018.
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