{
  "abstract": "Objectives IgA2 anti-dsDNA has recently emerged as a biomarker of response to combination therapy in systemic lupus erythematosus (SLE). We sought to investigate clinical correlates of IgA subclass anti-dsDNA antibodies in a large cohort of lupus patients who were refractory to conventional immunosuppressive therapy.Methods Serum levels of C3, C4, and anti-dsDNA autoantibody titres were assessed in a UK registry of biologic-treated SLE patients (BILAG-BR; n=105) and a single centre cohort with milder disease (n=59). IgA1 and IgA2 anti-dsDNA were measured using an in-house ELISA, while C3, C4, and IgG anti-dsDNA were obtained from routine clinical assays. Statistical analyses included Fisher’s exact test, Kruskal-Wallis test and logistic regression.Results Among the refractory BILAG-BR cohort, 40% were positive for IgA2 anti-dsDNA (AU >= 12.5), compared to 18.6% in the non-refractory cohort. Analysis of IgG, IgA1 and IgA2 anti-dsDNA autoantibodies in the refractory cohort revealed that IgG+IgA1-IgA2- anti-dsDNA was the most common (n=36), followed by triple-positive IgA1+IgA2+IgG+ anti-dsDNA (n=29). Compared with IgG+IgA1-IgA2- and other antibody groups, triple-positive IgG+IgA1+IgA2+ individuals had significantly higher proportions of low C4 (86% in IgG+IgA1+IgA2+ vs 48% in IgG+IgA1-IgA2- vs 44% in others, p = 0.00294) and low C3 (79% in IgG+IgA1+IgA2+ vs 39% in IgG+IgA1-IgA2- vs 15% in others, p = 0.00386). Patients in the triple-positive cohort also had significantly higher BILAG disease activity compared to IgG+IgA1-IgA2- patients as defined by the numerical BILAG scoring system (p = 0.043). Triple-positive antibody status (IgG+IgA1+IgA2+) conferred the highest risk of severe renal disease (OR=4.91, p=0.003), followed by single IgG-anti-dsDNA antibody positivity (OR=3.75, p=0.008) compared to other antibody profiles.Abstract PO:08:222 Figure 1Conclusions SLE patients with concurrent IgG, IgA1, and IgA2 anti-dsDNA antibodies represent a distinct, high-risk subgroup characterised by hypocomplementemia, heightened disease activity, and an increased risk of active renal involvement. These findings indicate that triple-positive anti-dsDNA status may serve as a valuable biomarker for disease stratification in severe SLE.Figure 1. Triple-positive anti-dsDNA defines a subset of patients with severe disease. (A) IgA1/IgA2/IgG anti-dsDNA autoantibodies in refractory SLE patients. (B) Association of low C4 and autoantibody status. (C) Association of low C3 and autoantibody status. (D) Total numerical BILAG score by autoantibody status.",
  "authors": [
    {
      "affiliations": [
        "University College London, Division of Medicine, London, UK"
      ],
      "name": "Claire Beesley"
    },
    {
      "affiliations": [
        "University College London, Division of Medicine, London, UK"
      ],
      "name": "Dylan Kotecha"
    },
    {
      "affiliations": [
        "University College London, Division of Medicine, London, UK"
      ],
      "name": "Daniel Mccluskey"
    },
    {
      "affiliations": [
        "The University of Manchester, Division of Musculoskeletal and Dermatological Sciences., Manchester, UK"
      ],
      "name": "Mia Rodziewicz"
    },
    {
      "affiliations": [
        "The University of Manchester, Division of Musculoskeletal and Dermatological Sciences., Manchester, UK"
      ],
      "name": "Emily Sutton"
    },
    {
      "affiliations": [
        "The University of Manchester, Division of Musculoskeletal and Dermatological Sciences., Manchester, UK"
      ],
      "name": "Ian Bruce"
    },
    {
      "affiliations": [
        "University College London, Division of Medicine, London, UK"
      ],
      "name": "Muhammad Shipa"
    },
    {
      "affiliations": [
        "University College London, Division of Medicine, London, UK"
      ],
      "name": "Michael Ehrenstein"
    }
  ],
  "title": "PO:08:222 Triple-positive IgG, IgA1, and IgA2 anti-dsDNA autoantibodies identify a high-risk subgroup in refractory SLE",
  "uid": "73458e82-7049-5d06-b6a9-3503cad55d13"
}