sIL7R concentrations in the serum reflect disease activity in the lupus kidney

Abstract

Objectives

Evaluation of disease activity in systemic lupus erythematosus (SLE) nephritis is a challenge, and repeated renal biopsies are usually needed in order to confirm a suspicion of flare. In a previous cross-sectional study, we reported that serum soluble form of the interleukin-7 receptor (sIL7R) levels is strongly associated with nephritis in SLE patients. In the present study, we wanted to confirm the association between changes in serum sIL7R concentrations and renal disease activity in a large longitudinal cohort of SLE nephritis patients.

Methods

Sera were harvested longitudinally in 105 SLE nephritis patients. Serum sIL7R cut-off value for the detection of SLE nephritis activity was determined as the mean sIL7R concentration in non-nephritis SLE patients + 2 SDs using data collected in our previous study. Patients with glomerular filtration rate (GFR) <60 mL/min/1.73 m ² (n=17) were excluded from the study due to persistently elevated serum sIL7R values.

Results

Serum sIL7R concentrations above the renal cut-off value were observed in 25 (out of 88) patients with a normal GFR. These patients had significantly higher serum double-stranded DNA (dsDNA) Ab and urinary protein to creatinine (UPC) ratio. Strikingly, 12 of them developed a renal British Isles Lupus Assessment Group index (BILAG) A within the next 3 months, while this was only the case in four out of the 63 other patients (p<0.0001). The test had 75.0% sensitivity and 81.9% specificity for the detection of a renal BILAG A. Combination of serum sIL7R with any of the classical tests (anti-dsDNA Ab titres, UPC ratio, serum C3) resulted in an increased specificity for the detection of a renal flare. Administration of immunosuppressive therapy resulted in a significant decrease in serum sIL7R concentrations.

Conclusions

Serum sIL7R is a sensitive and specific marker of renal disease activity in SLE. Elevated serum sIL7R values in SLE patients are associated with or predict the occurrence of an SLE nephritis flare.