{
  "abstract": "Objectives Some ANA+ (at risk) individuals develop SLE. Previous studies failed to demonstrate differences in autoantibody profile among progressors but were limited by insensitivity of routine assays. We applied a more sensitive measure of autoantibody specificities to an at-risk cohort.Methods ANA+ individuals identified by Bioplex 2000 were referred to secondary care with non-specific symptoms but not classifiable SLE. 32 healthy ANA- individuals and 72 established SLE patients were included as comparators. Progression was defined as classifiable SLE within three years. Levels of ANA specificities were analysed using addressable laser bead immunoassay (FIDIS Connective, Biosynex, France) modified to obtain strictly quantitative low levels for ten ANA specificities (Ro52, Ro60, SSB, Sm, U1RNP, SmRNP complex, dsDNA, histone, ribosomal P and PCNA), and their content in immune complexes (IC) was measured after purification and dissociation. Total serum C1q-binding IC were quantified with ELISA,Results Of 308 at-risk individuals, 47 developed SLE (progressors) while 261 did not (non-progressors). While levels were mostly within the conventional normal range, all SLE-related autoantibodies except Ro52, Ro60, SSB and PCNA were higher at baseline in the progressors vs. non-progressors. Serum anti-Sm was the strongest factor, distinguishing progressors from non-progressors at an optimal cut-off at 40% of the cut-off used to distinguish SLE patients from healthy individuals ( figure 1A). Using this cut-off, 15/47 progressors and 8/261 non-progressors were anti-Sm positive (OR 14.8 [CI 5.8-37.7]). Anti-dsDNA in serum was the second-best predictor (figure 1B). Sixten non-progressors and 17 progressors had either anti-Sm or anti-dsDNA using optimal cut-offs (OR 8.7 [4.0-19.0]). 2 non-progressors and 9 progressors had both antibodies (OR 30.7 [6.4-147]). Levels of autoantibodies within IC did not improve prediction models.Abstract PT5:01 Figure 1Differences in autoantibody levels within the normal range predict future SLE. anti-Sm and anti-dsDNA levels in non-progressors, SLE progressors, patients with manifest SLE and healthy controls, with the conventional cut-off previously defined as the 98th percentile of 200 healthy blood donors (=1AU/ml for both anti-Sm and anti-dsDNA), together with optimal cut-offs for differentiating progressors and non-progressorsConclusions Differences in autoantibody levels below the levels usually reported by clinical laboratories predict progression to SLE in an at-risk cohort. This suggests subtle alterations in the B cell repertoire immediately before disease development. Screening in a preclinical disease population could predict SLE with adjusted sensitivity and thresholds. Individuals with either anti-Sm or anti-dsDNA should be followed closely for future progression, while the combination of anti-Sm and anti-dsDNA and other biomarkers might identify individuals suitable for preclinical SLE-prevention studies.",
  "authors": [
    {
      "affiliations": [
        "Dept of Rheumatology and Inflammation Research, Inst of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Marit Stockfelt"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"
      ],
      "name": "Marina Barguil Marcedo"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"
      ],
      "name": "Han Hua Yu"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"
      ],
      "name": "Md Yuzaiful Md Yusof"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"
      ],
      "name": "Jack Arnold"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"
      ],
      "name": "Lucy Marie Carter"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"
      ],
      "name": "Zoe Wigston"
    },
    {
      "affiliations": [
        "Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Anna Svanqvist"
    },
    {
      "affiliations": [
        "Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Christine Möller Westerberg"
    },
    {
      "affiliations": [
        "Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Johan Rönnelid"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"
      ],
      "name": "Edward Vital"
    }
  ],
  "title": "PT5:01 Differences in autoantibody levels within the normal range predict future SLE in an at-risk cohort",
  "uid": "40e2051b-6afe-5d4b-9ef3-f7b6cc49b38d"
}