{
  "abstract": "Objectives NETs are elevated in SLE, correlating with disease activity and cardiovascular co-morbidity. We aimed to evaluate whether NETs were increased in ANA+ at-risk individuals, or predicted progression to classifiable SLE.Methods 144 ANA+ individuals referred with new symptoms of suspected SLE were followed yearly, up to 36 months and classified as progressors or non-progressors based on the 2019 EULAR/ACR SLE criteria. At each visit, clinical and laboratory data were recorded, and sera were collected and stored. ELISAs for myeloperoxidase (MPO) and citrullinated histone 3 (citH3) conjugated with deoxynucleic acid (DNA), key components of NETs, were performed on the baseline sample, as well as in 22 healthy controls (HC). Non-parametrical statistical tests were applied with alpha=0.05.Results MPO-DNA and citH3-DNA were higher in progressors (N = 30) compared to HC (median 295 AU versus 96 AU, p=0.015, and 336 AU versus 209 AU, p=0.045, respectively), but also numerically or significantly higher in non-progressors (214 AU, ns; 289 AU, p = 0.013, respectively). Among progressors, baseline MPO-DNA correlated with total IgG levels (rho = 0.385, p = 0.035), and was higher in dsDNA Ab+ individuals (p = 0.028), but not related to IFN-I scores at baseline. Progressors with leuko/lymphopenia at 12 months had higher MPO-DNA at baseline (p = 0.040). Within progressors, citH3-DNA was higher in those positive for rheumatoid factor at baseline (p = 0.028), and those that developed xerostomia at 12 months (p = 0.050). In the entire at-risk cohort, higher MPO-DNA titres at baseline associated with leuko/lymphopenia (p = 0.014), thrombocytopenia (p = 0.022), and arthritis (p = 0.049) at 24 months, and sicca symptoms (xerostomia: p = 0.046; xerophthalmia: p = 0.044) at 36 months.Conclusions Serum NETs are increased in the ANA+ at-risk stage of autoimmunity with or without progression to SLE, corroborating this as a state of profound innate immune dysregulation that could influence long-term health regardless of SLE diagnosis. Associations between NETs and clinical and laboratory features of SLE and Sjogren’s disease support their role in pathogenesis of progression. This role may be independent of IFN-I pathway activation.",
  "authors": [
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Marina Barguil Macedo"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Samuel Wood"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Lucy Carter"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Jack Arnold"
    },
    {
      "affiliations": [
        "University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Marit Stockfelt"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Md Yuzaiful Md Yusof"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Martin Stacey"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Edward Vital"
    }
  ],
  "title": "PO:02:060 Neutrophil extracellular traps (NETs) serum levels are increased in ANA positive at-risk individuals and are associated with features of systemic lupus erythematosus",
  "uid": "1ddc4fa7-1e50-5e8b-8781-d8ea7b3d4bba"
}