Background/Purpose:

B-lymphocytes have a pivotal role in the pathogenesis of Systemic Lupus Erythematosus (SLE). B-Lymphocyte Stimulator (BLyS) has an important role in the activation, differentiation and maintenance of activated B-cells. A PRoliferation Inducing Ligand (APRIL) is involved in the induction and maintenance of B- and T-cell responses. The aim of our study was to assess serum levels of BLyS and APRIL in patients with lupus nephritis (LN) and investigate how these levels are affected by immunosuppression.

Methods:

Sixty-four patients with biopsy-proven LN (52 proliferative nephritis, PN, and 12 membranous nephritis, MN) and 64 gender- and age-matched controls were included in our study (mean age 34 years). The patients were treated with corticosteroids combined with cyclophosphamide (CYC, n=45), mycophenolate mofetil (n=11), rituximab (n=7) or azathioprine (n=1) and underwent a second renal biopsy after completed induction therapy. Serum was collected before and after induction treatment (mean time 8 months) for the patients and at recruitment for the controls. The mean proteinuria at baseline was 2.2 g/d. BLyS and APRIL levels were estimated by ELISA (R&D Systems and eBioscience, respectively). The renal biopsies were assessed according to the ISN/RPS classification system, as well as Activity Index (AI) and Chronicity Index (CI). We defined clinical response (CR) as ≥50% reduction in proteinuria, normal or improved renal function (≥25% increase of GFR) and inactive urinary sediment. For complete response the proteinuria at follow-up should be <0.2 g/d and for partial response between 0.2 and 2 g/d. We defined histopathological response (HR) as ≥50% improvement in AI for partial response and additionally demanded a lack of signs for active inflammation (ISN/RPS class I, II, III C or IV C) in the follow-up biopsy for complete response.

Results:

BLyS levels were significantly higher in patients with LN than in controls (p<0.001), but remained unchanged after induction treatment (p=0.99). APRIL levels were significantly higher in patients compared to controls at baseline (p=0.005), but not at follow-up (0.14). This is consistent with a significant reduction of APRIL levels at follow-up (p<0.001). This decrease was more prominent in patients who received CYC (p=0.006). APRIL levels decreased significantly in both responding and non-responding patients. In the patient group with PN, the decrease of APRIL in non-responding patients was not statistically significant (p=0.13). Interestingly, the ROC-curve for BLyS by treatment response revealed a potential predictive power. Further analysis showed that low baseline levels of BLyS had high positive predictive value for both CR and HR.

Conclusion:

We observed an overall decrease in serum levels of APRIL after immunosuppression. No decrease was found in non-responding patients with PN, implying that APRIL could be of importance in this subgroup. BLyS levels remained unchanged after immunosuppressive treatment, suggesting that conventional treatments do not affect BLyS-producing cells. However, low baseline levels of BLyS were found to predict both CR and HR, suggesting that BLyS should be evaluated as a potential biomarker of response in LN.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-lymphocyte-stimulator-and-a-proliferation-inducing-ligand-in-lupus-nephritis-low-serum-levels-of-blys-predict-treatment-response/