Increased expression of soluble inducible costimulator ligand (ICOSL) in patients with systemic lupus erythematosus

Abstract

To investigate the level of costimulating molecules in systemic lupus erythematosus (SLE), we assessed the plasma concentrations of soluble forms of costimulatory molecules such as programmed death-1 (PD-1), B7-H1 (also called PD-L1 or CD274) and inducible costimulator ligand (ICOSL) in patients with SLE. Plasma concentrations of soluble PD-1, B7-H1 and ICOSL were measured by ELISA using plasma samples from 57 SLE patients with or without the active disease, 21 rheumatoid arthritis (RA) patients and 35 healthy subjects. We also evaluated surface ICOSL expression on B cells using flow cytometry to gain a better understanding of ICOSL expression. To compare the level of ICOSL mRNA expression, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using total RNA from peripheral blood mononuclear cells (PBMCs) isolated from eight healthy subjects and 11 patients with SLE. The concentration of plasma ICOSL was significantly higher in patients with SLE compared with healthy subjects (P = 0.005). Plasma ICOSL concentrations in patients with active SLE were also significantly higher than those of either patients with inactive SLE or patients with RA (P = 0.001, P = 0.015, respectively). Plasma ICOSL concentrations in patients with SLE correlated modestly with the SLE disease activity index score (r = 0.298, P = 0.024). We also found a significant inverse correlation between the soluble ICOSL expression and the surface ICOSL expression on B cells (r = −0.690, P = 0.001). However, ICOSL mRNA levels of patients with SLE were comparable with those of the control subjects. There was also no significant difference in plasma B7-H1 concentrations between groups, and plasma PD-1 was not detectable in any of the groups. The plasma concentration of soluble ICOSL might be correlated to the disease severity of lupus. The increased levels of ICOSL in active lupus suggest that this pathway is involved in the pathogenesis of SLE. The mechanism and physiological role of soluble ICOSL in the pathogenesis of SLE, however, remains to be investigated.

Keywords

inducible T-cell costimulator ligand systemic lupus erythematosus

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