title: Increased concentration of plasma TNFR1 and TNFR2 in paediatric lupus nephritis.
abstract: BACKGROUND
  Juvenile-onset systemic lupus erythematous (JSLE) is a debilitating condition that frequently involves the kidneys (lupus nephritis; LN). Tumour necrosis factor alpha (TNF-α), an important pro-inflammatory cytokine, is expressed locally in the kidney and correlates with LN disease activity. The aim of this study was to ascertain whether soluble receptors for TNF-α (sTNFR1/sTNFR2) are significantly increased in children with LN.
  
  
  METHODS
  Plasma samples were collected from JSLE patients at routine review. Concentrations of sTNFR1 and sTNFR2 were measured (median; interquartile range, IQR) using enzyme-linked immunosorbent assay (ELISA) in 25 JSLE patients (seven LN) and 20 healthy controls (HCs).
  
  
  RESULTS
  sTNFR2 concentration was significantly increased in JSLE (5149 pg/dl, 3413-8561) compared to HCs (3858 pg/dl, 2254-5165; p = 0.049). sTNFR1 concentration was significantly increased in active LN (n = 7, 1765 pg/dl, IQR 1133-4167) compared to inactive LN (n = 18, 1104 pg/dl, 886-1272; p = 0.018). There was a non-significant increase in sTNFR2 concentration in active LN (9829 pg/dl, 3298-21271) compared to inactive LN (4595 pg/dl, 3345-6993; p = 0.146). sTNFR1 concentration correlated moderately with sTNFR2 (r = 0.66, p < 0.001). sTNFR2 demonstrated strong positive correlations with ESR (r = 0.941, p < 0.01) and anti-dsDNA antibodies (r = 0.998, p = 0.041). Both receptors also positively correlated with creatinine (TNFR1 r = 0.81, p < 0.001; TNFR2 r = 0.50, p = 0.015) and urinary albumin creatinine ratio (TNFR1 r = 0.64, p < 0.01; TNFR2 r = 0.63, p < 0.01).
  
  
  CONCLUSIONS
  These data indicate that sTNFR1 and sTNFR2 concentrations are elevated in LN and may reflect renal activity. These results provide basis for further investigation into the pathological pathways underlying LN.
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, UK.
authors: M
authors: M
authors: Patel
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, UK Department of Paediatric Nephrology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK Louise.Oni@liverpool.ac.uk.
authors: L
authors: L
authors: Oni
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, UK.
authors: A
authors: A
authors: Midgley
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, UK Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors: E
authors: E
authors: Smith
authors: Department of Paediatric Nephrology, Great Ormond Street Children's NHS Hospital, London, UK.
authors: K
authors: K
authors: Tullus
authors: Department of Paediatric Nephrology, Great Ormond Street Children's NHS Hospital, London, UK.
authors: S D
authors: SD
authors: Marks
authors: Department of Paediatric Nephrology, Great Ormond Street Children's NHS Hospital, London, UK.
authors: C A
authors: CA
authors: Jones
authors: Department of Rheumatology, Great Ormond Street Children's NHS Hospital, London, UK.
authors: C
authors: C
authors: Pilkington
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, UK Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors: M W
authors: MW
authors: Beresford
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D003404:Creatinine / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000097:blood* / Q000652:urine; D008297:Male; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012709:Serum Albumin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012709:Serum Albumin; C506235:TNFRSF1A protein, human; C415902:TNFRSF1B protein, human; D003404:Creatinine
keywords: Nephritis; renal lupus; systemic lupus erythematosus