Session Information
Date: Monday, November 9, 2015
Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). Renal biopsy is gold standard for evaluation of renal activity and damage. New non-invasive biomarkers are warranted. Axl belongs to the Thyro3-Axl-Mer receptor tyrosine kinase subfamily and is mainly expressed on antigen presenting cells. Tumor Necrosis Factor Receptors (TNFRs) are involved in the pathogenesis of SLE. In previous reports, levels of the soluble forms of Axl and TNFRII were elevated in SLE patients, and Axl levels correlated with disease activity. The role of these molecules in LN remains to be clarified.
Methods: Serum levels of Axl and TNFRII were assessed by ELISA (R&D Systems) in 64 patients with biopsy-ascertained active LN before and after induction treatment. Follow-up renal biopsies were performed after a mean time of 8.1 months. Reduced proteinuria by ≥50%, normal or improved estimated Glomerular Filtration Rate (eGFR) by ≥25%, and inactive urinary sediment signified clinical responders (CR). Improvement of Activity Index (AI) in the follow-up renal biopsies by ≥50% signified histopathological responders (HR). Long-term renal outcome after a mean time of 10.9 years was determined by the last eGFR.
Results: Serum levels of Axl and TNFRII declined following induction therapy for LN in both CR and HR (p<0.005). In clinical non-responders (CNR), Axl levels remained unchanged while TNFRII levels declined (p=0.049). In histopathological non-responders (HNR), Axl levels remained stable while TNFRII levels declined (p=0.008).
In patients with proliferative LN (PLN; n=52), Axl and TNFRII levels declined in both CR and HR (p<0.005). Axl levels remained stable in CNR and HNR while TNFRII levels declined (p<0.05).
In patients with membranous LN (MLN; n=12), Axl and TNFRII levels declined in CR (p<0.05), but not in CNR. TNFRII levels declined in HR (p=0.046), but not in HNR, while Axl levels remained stable both in HR and HNR.
Baseline Axl and both baseline and follow-up TNFRII levels correlated inversely with the last eGFR (p=0.014, r=–0.307; p=0.021, r=–0.290; p=0.043, r=–0.256, respectively). Baseline TNFRII levels correlated with AI in baseline biopsies (p=0.026, r=0.279) and both baseline and follow-up Chronicity Index (CI) scores (p=0.012, r=0.313 and p=0.003, r=0.373, respectively). TNFRII levels correlated with CI at follow-up (p<0.001, r=0.535). Both baseline and follow-up Axl levels correlated with follow-up CI scores (p=0.022, r=0.289 and p=0.037, r=0.264, respectively).
Conclusion: Our data suggest Axl as a candidate biomarker of renal activity and treatment response in PLN and TNFRII as a candidate biomarker of renal activity and response in MLN. Higher baseline Axl and TNFRII levels were associated with unfavorable long-term renal outcome, supporting a role of these molecules in more severe renal disease and a more unfavorable prognosis. Moreover, our data suggest Axl as a candidate biomarker of renal damage in LN patients after induction therapy and TNFRII as a biomarker of both renal activity and damage in LN.
To cite this abstract in AMA style:
Parodis I, Ding H, Zickert A, Mohan C, Gunnarsson I. Serum Axl and Tumor Necrosis Factor Receptor II Portend Long-Term Renal Outcome in Lupus Nephritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/serum-axl-and-tumor-necrosis-factor-receptor-ii-portend-long-term-renal-outcome-in-lupus-nephritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-axl-and-tumor-necrosis-factor-receptor-ii-portend-long-term-renal-outcome-in-lupus-nephritis/