THU0250 URINE AND SERUM S100 PROTEINS ASSOCIATE WITH LUPUS NEPHRITIS AND RESPONSE TO TREATMENT
Authors: J. Davies, A. Midgley, S. Donohue, I. N. Bruce, M. Beresford, C. Hedrich
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Approximately 30% of SLE patients develop lupus nephritis (LN) that affects treatment and prognosis. Easily accessible biomarkers do not exist to reliably predict renal disease 1 . Recently, calcium-binding S100 proteins have been suggested as biomarkers in systemic inflammatory conditions, including SLE 2,3 . Objectives: The MASTERPLANS Consortium aims to identify indicators of treatment responses in SLE. This study tested the applicability of S100 proteins in serum and urine as biomarkers for disease activity and response to treatment with rituximab in LN. Methods: S100A8/A9 and S100A12 proteins were quantified in the serum and urine of 243 SLE patients from the BILAG-BR study and 48 matched controls using MSD technology to determine whether they perform as biomarkers for active LN (n=85 SLE patients) and/or may be used to predict response to treatment with rituximab. Renal disease activity and response to treatment was based on BILAG-BR scores and changes in response to treatment 4,5 . Results: Serum S100A12 (p&lt;0.001), and serum and urine S100A8/A9 (p&lt;0.001) are elevated in SLE patients. While serum and urine S100 levels do not correlate with global SLE disease activity (SLEDAI), levels in urine and urine/serum ratios are elevated in SLE patients with active LN (S100A8/A9: urine p&gt;0.005, urine/serum p&lt;0.05; S100A12: urine p&lt;0.05, serum/urine p&lt;0.005). S100 proteins perform better as biomarkers for active LN involvement in SLE patients positive for anti-dsDNA antibodies. Lastly, binary logistic regression and AUC analysis suggests the combination of serum S100A8/A9 and S100A12 to predict response to RTX treatment in LN after 6 months. Conclusion: Findings from this study show promise for clinical application of S100 proteins to predict active renal disease in SLE and response to treatment with rituximab. Significantly overlapping values between groups currently prohibit the definition of cut-off values and prospective studies are required to validate findings. References: [1]Reppe Moe SE, et al . Assessing the relative impact of lupus nephritis on mortality in a population-based systemic lupus erythematosus cohort. Lupus . 2019;28(7):818-825. [2]Austermann J, et al . S100 proteins in rheumatic diseases. Nat Rev Rheumatol . 2018;14(9):528-541. [3]Tydén H, et al . Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus. Lupus . 2017;26(2):139-149. [4]Yee CS, et al . Numerical scoring for the BILAG-2004 index. Rheumatology. 2010; 49(9):1665-1669. [5]McCarthy et al . Short-term efficacy and safety of rituximab therapy in refractory systemic lupus erythematosus: Results from the british isles lupus assessment group biologics register. Rheumatol . 2018;57(3):470-479. Acknowledgments: Clinical information and serum/urine samples from SLE patients were provided by BILAG-BR centres. Disclosure of Interests: Jennifer Davies: None declared, Angela Midgley: None declared, Sean Donohue: None declared, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GSK, and UCB, Consultant of: Eli Lilly, AstraZeneca, UCB, Iltoo, and Merck Serono, Speakers bureau: UCB, Michael Beresford: None declared, Christian Hedrich Grant/research support from: Research grant support from Novartis (Molecular pathophysiology of psoriasis)., Speakers bureau: Speaker honoraria from Roche (pathophysiology of polyarticular JIA and systemic JIA); involved in advisory boards for Novartis (systemic JIA and IL-1 mediated diseases).