{
  "abstract": "Objectives Complement activation plays a dual role in systemic lupus erythematosus (SLE) and lupus nephritis (LN) pathogenesis: protective through clearance of immune complexes and cellular waste, but damaging when uncontrolled activation promotes kidney injury. While complement dysregulation is recognized in SLE, mechanisms influencing LN activity remain poorly understood. We evaluated circulating and excreted complement activation and regulatory markers in relation to SLE and LN activity, and treatment response in active LN.Methods We analysed classical and alternative complement pathway activation and regulatory protein concentrations in matched serum and urine samples from 21 SLE patients with active biopsy-proven LN (19 from Saint-Luc University Hospital, Brussels; 2 from Karolinska University Hospital, Stockholm), 20 SLE patients without LN (10 active, 10 in remission), and 15 healthy controls from Karolinska University Hospital. LN samples were collected before immunosuppressive therapy (T0) and after one year (T1). Complement proteins Ba, Bb, C3a, C4a, C5a, sC5b-9, factor H, and factor I were assessed using Quidel MicroVue Multiplex Complement Array. Serum levels were normalised to the median HC concentration. Urine concentrations were normalized to urinary creatinine (ng protein/mg creatinine). The Mann-Whitney U test was used to compare protein levels between groups.Results Serum C4a and sC5b-9 were significantly higher in LN patients versus SLE without LN or HC (p<0.001 and p<0.0001; p<0.05 and p<0.01, respectively), while serum C3a, factor I, and factor H were higher in SLE without LN (p<0.05, p<0.001, p<0.01). After one year of immunosuppressive therapy, LN patients showed significantly reduced serum Ba (p<0.001), Bb (p<0.01), sC5b-9 (p<0.001), factor I (p<0.01), factor H (p<0.05), and C5a (p<0.05). Urine analysis revealed significantly elevated complement proteins in LN patients versus SLE without LN and HC (p<0.0001). Urine Ba and C5a decreased significantly after one year of therapy (p<0.05). Complement activation did not differ between active and remission SLE.Abstract PO:01:004 Figure 1Conclusions Elevated urine levels of complement activation and regulatory markers are characteristic of SLE patients with LN. Serum levels of Ba, Bb, sC5b-9, factor I, factor H, C5a, and urine levels of Ba and C5a were significantly reduced following therapy, suggesting their potential as biomarkers of renal activity.",
  "authors": [
    {
      "affiliations": [
        "Karolinska Institutet and Karolinska University Hospital, Division of Rheumatology, Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Natalia Sherina"
    },
    {
      "affiliations": [
        "Karolinska Institutet and Karolinska University Hospital, Division of Rheumatology, Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Denis Lagutkin"
    },
    {
      "affiliations": [
        "Karolinska Institutet and Karolinska University Hospital, Division of Rheumatology, Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Robert Tonoian"
    },
    {
      "affiliations": [
        "Karolinska Institutet and Karolinska University Hospital, Division of Rheumatology, Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Dionysis Nikolopoulos"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Division of Rheumatology, Baltimore, USA",
        "Catholic University of Louvain, Department of Inflammatory and Systemic Rheumatic Diseases, Institute of Experimental a, Brussels, Belgium"
      ],
      "name": "Andrea Fava"
    },
    {
      "affiliations": [
        "Catholic University of Louvain, Department of Inflammatory and Systemic Rheumatic Diseases, Institute of Experimental a, Brussels, Belgium",
        "Saint-Luc University Hospital, Department of Rheumatology, Brussels, Belgium"
      ],
      "name": "Farah Tamirou"
    },
    {
      "affiliations": [
        "Catholic University of Louvain, Department of Inflammatory and Systemic Rheumatic Diseases, Institute of Experimental a, Brussels, Belgium",
        "Saint-Luc University Hospital, Department of Rheumatology, Brussels, Belgium"
      ],
      "name": "Frédéric A Houssiau"
    },
    {
      "affiliations": [
        "Karolinska Institutet and Karolinska University Hospital, Division of Rheumatology, Department of Medicine Solna, Stockholm, Sweden",
        "Örebro University, Department of Rheumatology, Faculty of Medicine and Health, Örebro, Sweden"
      ],
      "name": "Ioannis Parodis"
    }
  ],
  "title": "PO:01:004 Urine levels of complement proteins differentiate lupus nephritis from non-renal systemic lupus erythematosus",
  "uid": "9caa8623-08e0-554a-96ed-96f333d86a1a"
}