Background Evaluation of disease activity in 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 high serum soluble IL-7 receptor (sIL7R) concentrations result from a local production of the molecule in the lupus kidney, upon stimulation by pro-inflammatory cytokines. Elevated serum sIL7R levels are therefore strongly associated with nephritis in SLE patients, and correlate with SLEDAI scores. 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, followed at a single centre.
Methods Sera were harvested longitudinally in 105 SLE nephritis patients from July, 2012 and stored at -80°. Median number of serum samples/patient was 3 (range 1-7); median follow-up was 15 months (range 1-19); median interval between serum samples was 5 months (range 2-14). Serum sIL7R concentrations were determined by ELISA. Serum dsDNA antibody (Ab) titers, serum C3 concentrations, urinary protein/creatinine (UPC) ratios and clinical data were retrieved from the medical records at the same time points. 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 standard deviations, using data collected in our previous study. Patients with glomerular filtration rate <60 ml/min. were excluded from the study, due to persistently elevated serum sIL7R values.
Results Serum sIL7R concentrations above the cut-off value were observed in 25 (out of 88) different patients. In some patients, elevated values were detected in several longitudinal measurements. Patients with elevated serum sIL7R concentrations had significantly higher serum dsDNA Ab titers (median: 57 U/ml, range: 5.3 – 2,107 U/ml versus median: 11.4 U/ml, range: 0 – 558 U/ml, p =0.03 by Mann-Whitney test) and UPC ratios (median: 0.26, range: 0.05 – 3.69 versus median: 0.14, range: 0.03 – 4.30, p =0.01 by Mann-Whitney test) at that time point, compared to patients with sIL7R concentrations below the cut-off value. Serum C3 concentrations were lower in patients with elevated sIL7R values (mean ± SEM: 79.0±6.4 mg/dl versus 90.2±2.9 mg/dl), but the difference did not reach statistical significance (p =0.07 by Student's t-test). Strikingly, 11 out of the 25 patients with high serum sIL7R levels developed a renal BILAG A at the time of or within the next 3 months following the abnormal measurement, while this was only the case in 4 out of the 63 other patients (p <0.0001 by Fisher's exact test). In patients with elevated sIL7R values, administration of immunosuppressive therapy resulted in a significant decrease in serum sIL7R concentrations, while this was not the case in patients not receiving any additional treatment.
Conclusions Serum sIL7R is a highly sensitive marker of renal disease activity in SLE. Elevated serum sIL7R values in SLE patients are associated with or predict the occurrence of a SLE nephritis flare.
Disclosure of Interest None declared