THU0522 Plasma TNFR1 and TNFR2 in Active Paediatric Lupus Nephritis
Authors: M. Patel, L. Oni, G. Jeffers, E. Smith, A. Midgley, K. Tullus, C. Pilkington, S. Marks, M. Beresford
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Juvenile systemic lupus erythematous (JSLE) is a debilitating condition that frequently involves the kidneys (lupus nephritis; LN). In LN up to 25% develop end stage renal failure within 10 years.<sup>[1]</sup> Our group have been investigating the urine biomarker monocyte chemoattractant protein-1 (MCP-1) and the tumour necrosis factor-alpha (TNF-a) pathway is believed to be involved in MCP-1 expression.<sup>[2]</sup> TNF-a acts via its receptors soluble tumour necrosis factor receptor 1 and 2 (TNFR1 and TNFR2). These are significantly elevated in adult LN.<sup>[3]</sup> These novel biomarkers have not been investigated in JSLE. <h3>Objectives</h3> The aim of this study is to ascertain whether sTNFR1 and sTNFR2 are significantly increased in children with LN. <h3>Methods</h3> Plasma samples were collected from patients recruited to the UK JSLE Cohort Study at routine review. Full ethical approval was attained. Concentrations of sTNFR1 and sTNFR2 were measured using enzyme linked immunosorbent assay (ELISA) in JSLE and healthy controls (HC). Active LN was defined as a renal British Isles Lupus Assessment group (BILAG) score of A/B and previous histological diagnosis. Inactive LN were scores D/E. Statistical analysis used Mann Whitney U and Pearsons correlations. <h3>Results</h3> Data is represented as median and interquartile ranges. There was a non-significant trend towards increased sTNFR1 in JSLE patients compared to HC (JSLE n=25, 1144pg/dl, 903-1617; HC n=20, 928pg/dl, 838-1143; <i>p=0.071</i>). sTNFR1 was significantly increased in active LN (n=7, 1765pg/dl, 1133-4167) compared to inactive LN (n=18, 1104pg/dl, 886-1272; <i>p=0.018</i>). sTNFR2 was significantly increased in JSLE (5149pg/dl, 3413-8561) compared to HC (3858pg/dl, 2254-5165; <i>p&lt;0.05</i>). There was no difference in sTNFR2 between active LN (9829pg/dl, 3298-21271) and inactive LN (4595pg/dl, 3345-6993; <i>p=0.146</i>). sTNFR1 positively correlated with sTNFR2 (r=0.663, <i>p&lt;0.001</i>). Both receptors positively correlated with creatinine (TNFR1 r=0.811, <i>p&lt;0.001</i>; TNFR2 r=0.50, <i>p=0.015</i>) and urinary albumin creatinine ratio (TNFR1 r=0.639, <i>p&lt;0.01</i>; TNFR2 r=0.627, <i>p&lt;0.01</i>). sTNFR2 positively correlated with ESR (r=0.840, <i>p&lt;0.01</i>). <h3>Conclusions</h3> This is the first study to investigate sTNFR1 and sTNFR2 in paediatric LN. They appear to have a pathophysiological role as they relate to LN disease activity and correlate with current clinical parameters. The receptors may have an upstream role in inducing MCP-1 production that could be used for early-targeted treatment and this is the focus of current research. Further investigation in a kidney cell line (such as podocytes) is warranted to attain a better understanding of different pathological pathways. <h3>References</h3> Mok, C. (2006) Therapeutic options for resistant lupus nephritis. Seminars in arthritis and rheumatism. 36, 71-81 Pai, R., Ha, H., Kirschenbaum, M. A and Kamanna, V.S (1996) Role of tumour necrosis factor-alpha on mesangial MCP-1 expression and monocyte migration:mechanisms mediated by signal transduction. joURNAL OF american Society of Nephrology: JASN. 7, 914-923 Mahmoud, R.A., El-Gendi, H. I. and Ahmed, H. H. (2005) Serum neopterin, tumour necrosis factor-alpha and soluble tumour necrosis factor II (p75) levels and disease activity in Egyptian female patients with systemic lupus erythematosus. Clinical biochemistry. 38, 134-141 <h3>Disclosure of Interest</h3> None declared