Marco Quaglia, Italy
Univerità del Piemonte Orientale Translational MedicinePresenter of 2 Presentations
CIRCULATING EXTRACELLULAR VESICLES HAVE HIGHER EXPRESSION OF COSTIMULATORY MOLECULES IN LUPUS NEPHRITIS
Abstract
Background and Aims
Extracellular vesicles (EV), microparticles mediating cell-to-cell communication, are involved in immunecomplexes deposition and renal damage in SLE. Aim of this study was to investigate the association between EV plasma levels, their profile of costimulatory molecules expression and presence and severity of Lupus Nephritis (LN).
Methods
Main clinical and laboratory parameters were compared among 67 SLE patients (52 with LN; 15 with rheumatological SLE) and 50 healthy controls (HCs). Plasma levels of EV were evaluated by Nanotrack; EVs were characterised by FACS analysis (20 surface molecules were considered, including ICOS/ICOS-L and PD-1/PD-1L). ICOS and ICOS-L serum levels were also measured (ELISA).
Results
Plasma EV levels and their dimensions were higher in SLE patients with LN as compared to those without LN (p<0.001 for both); no difference was found between pathological classes of LN. However, plasma EV levels correlated with proteinuria (p=0.032) and with SLICC at diagnosis. FACS analysis revealed a peculiar profile of several costimulatory molecules on EVs surface of patients with LN, with a progressively higher expression of ICOS-L, PD-1 and PD-1L moving from HCs to SLE without LN and then to SLE with LN.
Conclusions
Plasma EVs levels and dimensions and their expression of costimulatory molecules, such as ICOS/ICOS-L and PD-1/PD-1L, were higher in EVs from LN patients as compared with rheumatological SLE and HCs. These elements suggest that circulating EV with a peculiar profile of costimulatory molecules expression are involved in mechanisms of renal damage in SLE and may be promising as biomarkers and new therapeutic targets for LN.
THE ROLE OF ICOS/ICOS-L COSTIMULATORY PATHWAY AS BIOMARKER AND NEW THERAPEUTIC TARGET IN LUPUS NEPHRITIS
Abstract
Background and Aims
The costimulatory pathway ICOS/ICOS-L plays a key-role in cooperation between B and T lymphocytes and appears to be involved in SLE. The aim of this study was to evaluate the association between ICOS and ICOS-L plasma levels, their renal expression and presence and severity of Lupus Nephritis (LN).
Methods
Main clinical and laboratory parameters were compared among 67 SLE patients (52 with LN and 15 with rheumatological SLE) and 50 healthy controls (HCs). Plasma levels of ICOS/ICOS-L were assessed by ELISA and their renal expression by immunohistochemistry analysis.
Results
Plasma levels of ICOS and ICOS-L were significantly increased in SLE as compared with HCs (p<0.001) and were associated with disease duration (p=0.036 for ICOS and p<0.001 for ICOS-L), presence and severity of LN at diagnosis (p=0.017 and p=0.001 respectively), proteinuria (p=0.014 and p<0.001) and nephritic sediment (p=0.005 and p = 0.001). ICOS levels correlated with SLICC (p=0.027) and SLEDAI-2K (p=0.001) at diagnosis. At multivariate analysis only disease onset at younger age (p=0.018) and ICOS-L levels (p=0,047) were indipendently associated with LN. Immunohistochemistry analysis brought out a more intense ICOS-L tubular expression in proteinuric as compared with non-proteinuric LN (p<0,05), whereas glomerular expression was weak.
Conclusions
ICOS and ICOS-L plasma levels were increased in SLE and identified a subset of patients with long-lasting disease and severe LN at presentation. A more intense tubular expression of ICOS-L was present in proteinuric forms of LN. These elements suggest that ICOS/ICOS-L pathway is involved in pathogenesis of LN and is promising as a biomarker and therapeutic target.