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Abstract: FR-PO1072

Role of the ICOS/ICOS-L Costimulatory Pathway and of Circulating Extracellular Vesicles as Potential Biomarkers and New Therapeutic Targets in Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Cantaluppi, Vincenzo, University of Piemonte Orientale (UPO), Novara, Italy
  • Mazzariol, Martina, University of Piemonte Orientale, Novara , Novara, Italy
  • Merlotti, Guido, University of Piemonte Orientale, Novara, Italy
  • Quaglia, Marco, Università del Piemonte Orientale, Torino, Italy
Background

The costimulatory pathway ICOS/ICOS-L and extracellular vesicles (EV), microparticles known to have a role in cell-to-cell communication, both appear to be involved in tissue injury associated with SLE. The aim of this study was to evaluate the association between ICOS, ICOS-L or EV plasma levels and clinical expression of lupus nephritis (LN).

Methods

Main clinical and laboratory parameters were compared among 67 SLE patients (52 with LN and 15 with only rheumatological SLE) and 50 healthy controls. Plasma levels of ICOS/ICOS-L were assessed by ELISA and EV were evaluated by Nanotrack and FACS analysis.

Results

Serum levels of ICOS and ICOS-L were significantly increased in SLE as compared with healthy controls (p<0.001) and 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), proteinuria (p=0.014 and p<0.001) and nephritic sediment (p=0.005 and p=0.010). ICOS levels also correlated with established scores such as SLICC (p=0.027) and SLEDAI-2K (p=0.001) at diagnosis. At univariate logistic regression analysis, disease onset at younger age (p=0.007), ICOS (p=0.044) and ICOS-L levels (p=0.009) were associated with LN; however, at multivariate analysis only disease onset at younger age (p=0.018) and ICOS-L (p=0,047) were indipendently associated with renal involvement. Plasma EV levels were higher in SLE patients with LN (p<0.001) without discrimination between prolipherative and non-prolipherative classes: however, EV levels correlated with proteinuria (p=0.032) and ICOS levels (p=0.026). Of interest, FACS analysis revealed the presence of both ICOS and ICOS-L on EV surface.

Conclusion

ICOS and ICOS-L plasma levels are increased in SLE and appear to identify a subset of SLE patients with long-lasting disease and severe LN at presentation. In addition, plasma EV levels were also higher in SLE patients with LN and correlated with ICOS: circulating EV carried ICOS and ICOS-L proteins. ICOS/ICOS-L pathway and circulating EV may be potential biomarkers and new therapeutic targets in LN.