{
  "abstract": "Objectives To evaluate complement activation fragments (C3dg, C4d, soluble terminal complement complex [sTCC]) as biomarkers of systemic lupus erythematosus (SLE) disease activity and organ involvement, and to compare their performance with conventional C3 and C4 levels measured in the clinic.<FILE IMAGE=’17_20251019221708.jpg’>Methods The ACOMPLIS project (‘Assessing COMPLement activation In SLE’) is a multi-center, multi-laboratory study analyzing complement activation in paired and longitudinal SLE cohorts.In the Lund cohort, 95 patients (48 with lupus nephritis [LN], 47 with arthritis as a dominant symptom) provided plasma samples during active disease and low disease activity.In the longitudinal Swiss cohort (500 patients) complement markers were measured over sequential visits.EDTA plasma was analyzed in three independent laboratories using standardized assays: C3dg (neo-epitope TRIFMA and polyethylene glycol (PEG) precipitation), iC3b (lateral flow assay), C4d (neo-epitope ELISA), and sTCC (ELISA). Disease activity was assessed by SLEDAI and Physician’s Global Assessment (PGA). Associations were examined by non-parametric tests and linear mixed models.Results Upon reviewing all data, iC3b was excluded from analysis as even one freeze–thaw cycle markedly affected its stability.All other complement activation fragments were markedly elevated during active disease compared with remission (figure 1). Receiver-operating characteristic (ROC) analysis in the Lund cohort showed that each activation marker differentiated high from low disease activity (AUC 0.64–0.70), whereas C3 and C4 performed more weakly (AUC < 0.59).In the longitudinal Swiss cohort, C3dg, C4d, and sTCC correlated positively with SLEDAI over time (p < 0.001) and declined in DORIS remission.Patients with active LN had significantly higher levels of C3dg, C4d, and sTCC than non-renal patients. C3 performed well in differentiating active from non-active LN (AUC up to 0.86, p < 0.001) (figure 2). However, looking at odds ratios, C3dg and TCC performed best.The complement activation markers also associated with anti-dsDNA positivity and low complement by SLEDAI, confirming biological relevance.Abstract PO:02:030 Figure 1Differentiation between high and low disease activity (Lund cohort)Abstract PO:02:030 Figure 2Complement markers and association with Lupus nephritisConclusions Direct measurement of complement activation fragments provides a more accurate and dynamic reflection of lupus activity than conventional C3 and C4 levels.sTCC were particularly informative for both active SLE and nephritis. These results support integrating complement activation markers into future lupus disease-activity assessments and clinical monitoring frameworks.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology and Department of Biomedicine, Aarhus, Denmark"
      ],
      "name": "Anne Troldborg"
    },
    {
      "affiliations": [
        "Lund University, Lund, Sweden"
      ],
      "name": "Myriam Martin"
    },
    {
      "affiliations": [
        "Lund University, Lund, Sweden",
        "Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Anders Bengtsson"
    },
    {
      "affiliations": [
        "Lund University, Lund, Sweden",
        "Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Petrus Linge"
    },
    {
      "affiliations": [
        "Lund University, Lund, Sweden",
        "Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Andreas Jönsson"
    },
    {
      "affiliations": [
        "Department of Biomedicine, Aarhus University, Aarhus, Denmark"
      ],
      "name": "Annette Gudmann Hansen"
    },
    {
      "affiliations": [
        "Department of Biomedicine, Aarhus University, Aarhus, Denmark"
      ],
      "name": "Trine Korsgaard Hejlesen"
    },
    {
      "affiliations": [
        "Department of Biomedicine, Basel, Switzerland"
      ],
      "name": "Kristina Schulz"
    },
    {
      "affiliations": [
        "Department of Pathology and Immunology, University Hospital of Geneva, Geneva, Switzerland"
      ],
      "name": "Carlo Chizzolini"
    },
    {
      "affiliations": [
        "Rheumazentrum Ostschweiz, St. Gaellen, Switzerland"
      ],
      "name": "Johannes Von Kempis"
    },
    {
      "affiliations": [
        "Department of Nephrology and Hypertension, University Hospital of Bern, Bern, Switzerland"
      ],
      "name": "Uyen Huynh-Do"
    },
    {
      "affiliations": [
        "Washington University School of Medicine, St.Louis, USA"
      ],
      "name": "Alfred Kim"
    },
    {
      "affiliations": [
        "Washington University School of Medicine, St.Louis, USA"
      ],
      "name": "John Atkinso"
    },
    {
      "affiliations": [
        "Lausanne University Hospital, Lausanne, Switzerland"
      ],
      "name": "Camillo Ribi"
    },
    {
      "affiliations": [
        "Department of Biomedicine, Basel, Switzerland"
      ],
      "name": "Marten Trendelenburg"
    },
    {
      "affiliations": [
        "Lund University, Lund, Sweden"
      ],
      "name": "Anna Blom"
    },
    {
      "affiliations": [
        "Department of Biomedicine, Aarhus University, Aarhus, Denmark"
      ],
      "name": "Steffen Thiel"
    }
  ],
  "title": "PO:02:030 Direct measurement of complement activation in SLE outperforms C3/C4 as biomarkers of disease activity and lupus nephritis – results from the ACOMPLIS study",
  "uid": "a8eeb9ee-6c10-5c93-9116-f2c7c8cf1a0b"
}