OP0258 Efficacy of the highly selective adamts-5 inhibitor glpg1972 in the rat meniscectomy model

Lepescheux, L.; Clément-Lacroix, P.; Merciris, D.; Meurisse, S.; Borgonovi, Monica; Cottereaux, C.; Mollat, Patrick; Brebion, F.; Gosmini, Romain; Ceuninck, Frédéric De; Botez, Iuliana; Aar, Ellen van der; Christophe, Thierry; Vandervoort, Nele; Blanqué, R.; Comas, David Rigau; Deprez, Pierre; Amantini, David

doi:10.1136/annrheumdis-2018-eular.2610

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“…4 5 Objectives: In this communication we report the activity of GLPG1972 in a second model of surgery-induced OA, the rat meniscectomy (MNX) model. 6 Methods: OA pathology was induced by meniscectomy in the right hind leg of each rat. On day 1 post surgery, rats were randomly assigned to a treatment group (n=20 per group) according to their body weight.…”

Section: Discussionmentioning

confidence: 99%

OP0257 Decrease of autophagy in peripheral blood mononuclear cells from systemic lupus erythematosus patients treated with belimumab

Colasanti

Spinelli

Barbati

et al. 2018

Friday, 15 June 2018

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BackgroundAutophagy is a conserved catabolic process that degrades cytoplasmic constituents and organelles in the lysosome, promoting the recycling of cellular nutrients, and is also a key mechanism for protein homeostasis and quality control1.T lymphocytes from patients with systemic lupus erythematosus (SLE) are resistant to induction of autophagy2.Belimumab (BLM), a human monoclonal antibody that inhibits B lymphocyte stimulator (BLyS), is the first biological drug to be approved for the treatment of SLE. BLM seems to play a role in modulating the signalling cascade involved in the regulation of autophagy, blocking the binding of soluble BLyS to its receptors (B cell activating factor receptor, BAFF-R; B cell maturation antigen, BCMA; transmembrane activator and calcium modulator and cyclophilin ligand interactor, TACI), mainly expressed on B cells and plasmacells3.ObjectivesThe aim of this study was to evaluate the autophagy process by means the expression of LC3-II and p62 markers in lysates of peripheral blood mononuclear cells (PBMCs) from SLE patients at baseline (t0) and after 2 weeks (t2weeks), 1 month (t1month), and 3 months (t3months) of treatment with BLM. We also investigated the presence of BLyS receptors on T cell subsets.MethodsWe enrolled 15 consecutive patients who started treatment with BLM (M/F, 0/15; mean age, 44.3 years, range 30–54 years; mean disease duration, 242.6 months, range 48–432 months). All patients fulfilled the American College of Rheumatology revised classification criteria4. PBMCs from SLE patients were lysed in lysis buffer and analysed to evaluate autophagy, monitoring LC3-II and p62 levels by Western blot. Flow cytometry was performed for surface phenotyping of freshly isolated PBMCs, using conjugated monoclonal antibodies against human CD4 and CD8; anti-human BAFF-R, BCMA, and TACI polyclonal antibodies were used to detect BLyS receptors on T cells subsets.ResultsLC3-II expression levels in PBMCs from SLE patients decreased after 3 months of BLM therapy and, in the same lapse, p62 levels increased (figure 1; p<0.05 for all the experimental conditions). BAFF-R and BCMA were expressed on CD4+ (Mean Fluorescence Intensity -fold increase-, MFI=1.6 and 1.2, respectively; p<0.05) and CD8+ (MFI=1.6 and 2.5; p<0.05) T cells, while TACI was expressed only on CD8+ T cells (MFI=1.2; p<0.05).ConclusionsIn the present study we demonstrated, for the first time, the expression of BAFF-R, TACI and BCMA in CD4+ and CD8+ T cells from SLE patients, and that BLM treatment was able to decrease the levels of autophagy in PBMCs. We can speculate that BLM could mediate this effect by blocking the binding of BLyS with its receptors.References[1] Kaur, Debnath. Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol2015;16:461–72.[2] Alessandri, et al. T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy. FASEB J2012;26:4722–32.[3] Rockel, Kapoor. Autophagy: controlling cell fate in rheumatic diseases. Nat Rev Rheumatol2016;12:...

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Section: Discussionmentioning

confidence: 99%