Background Lupus nephritis (LN) affects up to 50% of patients with Systemic Lupus Erythematosus (SLE). The B-lymphocyte is pivotal in SLE and autoantibody production. B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) are important for the activation and maintenance of B-cells.
Objectives The aim of this study was to investigate serum levels of BLyS and APRIL in patients with LN, in order to clarify how these levels are affected by conventional immunosuppression. Through comparison with clinical data and correlation with autoantibodies, we further aimed to evaluate BLyS and APRIL as potential biomarkers for LN in comparison to conventional serology.
Methods Sixty-four patients with active biopsy-ascertained LN (52 proliferative LN, PLN; 12 membranous LN) and 64 individually matched controls were included. After induction therapy a follow-up biopsy was performed. Serum samples at baseline and follow-up were analyzed for BLyS, APRIL, autoantibodies and complement levels. The renal biopsies were assessed according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification system for LN1 and scored for Activity Index (AI) and Chronicity Index (CI)2. Clinical response (CR) was defined as ≥50% reduction in proteinuria, normal or improved renal function and inactive urinary sediment. Histopathological response (HR) required ≥50% improvement in AI.
Results Comparing patients to controls, baseline BLyS levels were significantly higher in patients (p<0.001) and remained unchanged after treatment. APRIL levels were significantly higher in patients at baseline (p=0.005), but not at follow-up. Among PLN patients, the decrease of APRIL was significant only in responders (p=0.009 for CR, p=0.01 for HR). Significant decreases of anti-dsDNA (p<0.001) and anti-C1q (p<0.001) were observed in PLN patients. Low baseline BLyS levels (<1.5 ng/mL) predicted treatment response, attaining a positive predictive value of 92% for CR among PLN patients.
No correlation was found between BLyS/APRIL and anti-dsDNA, anti-C1q, C3 or C4, at either baseline or follow-up. However, significant correlations were found between DBLyS and Danti-dsDNA in the combined patient group (rs=0.47, p<0.001), and among PLN patients (rs=0.49, p<0.001).
Conclusions Our results indicate that APRIL is of importance in PLN, and stress the need to evaluate BLyS as a candidate non-invasive prognostic biomarker of treatment response in LN.
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Disclosure of Interest : None declared