Article Text

PDF
THU0530 Blys and APRIL in Lupus Nephritis: Correlations with Serology - Blys as A Non-Invasive Predictor of Response
  1. I. Parodis1,
  2. A. Zickert1,
  3. M. Axelsson2,
  4. E. Svenungsson1,
  5. V. Malmström1,
  6. I. Gunnarsson1
  1. 1Department of Medicine, Rheumatology Unit, Karolinska Institutet
  2. 2AlbaNova, Stockholm University, Stockholm, Sweden

Abstract

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.

References

  1. Weening JJ, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Journal of the American Society of Nephrology: JASN. 2004 Feb;15(2):241-50.

  2. Austin HA, 3rd, et al. Prognostic factors in lupus nephritis. Contribution of renal histologic data. The American journal of medicine. 1983 Sep;75(3):382-91.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.3863

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.