THE ROLE OF ICOS/ICOS-L COSTIMULATORY PATHWAY AS BIOMARKER AND NEW THERAPEUTIC TARGET IN LUPUS NEPHRITIS
- Marco Quaglia, Italy
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.