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.

Keywords: Disease Activity; Lupus Nephritis; Systemic Lupus Erythematosus.

Figure 1

Biological indices of disease activity in a longitudinal cohort of SLE nephritis patients according to serum soluble form of the interleukin-7 receptor (sIL7R) concentrations. Anti-double-stranded DNA antibodies (A), urinary protein to creatine (UPC) ratio (B) and serum C3 (C) are plotted in patients with serum sIL7R concentrations above (sIL7R high, n=25) or below the renal cut-off (sIL7R low, n=63). p Values by Mann–Whitney U tests in (A) and (B), by Student's t test in (C).

Figure 2

Serum soluble form of the interleukin-7 receptor (sIL7R) longitudinal measurements in 88 patients with SLE nephritis. sIL7R serum concentrations are depicted in patients who will (A) (n=16) versus will not (B) (n=72) present a renal BILAG A during the time of the study. The time interval between two measurements is represented as an arbitrary unit, and varies between 2 and 14 (median 5) months. The dashed line represents the renal cut-off value for sIL7R serum concentrations (1042 pmol/mL).

Figure 3

Receiving operator characteristic (ROC) curves displaying the performances of serum soluble form of the interleukin-7 receptor (sIL7R) (A), serum anti-double-stranded DNA antibodies (B), serum C3 (C) and urinary protein to creatine (UPC) (D) measurements for the detection of a renal BILAG A in a cohort of SLE nephritis patients. The left panels show the variations in sensitivity and specificity of the indicated test according to several cut-off values. The dot surrounded by a circle corresponds to the cut-off values generally used for these tests (serum sIL7R=1042 pmol/mL; anti-double-stranded DNA antibodies=50 U/mL; serum C3=85 mg/dL; UPC ratio=0.5). The right panels show the ROC curves of the same tests (several cut-off values), when associated with the necessity of having a serum sIL7R value above the renal cut-off, for the detection of a renal BILAG A.

Figure 4

Evolution of elevated serum soluble form of the interleukin-7 receptor (sIL7R) concentrations in follow-up sera. Out of 25 patients with serum sIL7R values above the renal cut-off, 19 had at least one follow-up measurement (median follow-up: 3 months). Eight of them received immunosuppressive therapy for their renal BILAG A (A), and 11 did not (B). p Values by Wilcoxon matched-pairs signed rank test.