{
  "abstract": "Objectives Autoantibody profiling has revealed clinically meaningful systemic lupus erythematosus (SLE) subgroups in Caucasian descendant cohorts, contributing to decreased disease heterogeneity. Validation in non-European populations is essential for broader applicability. We aimed to define autoantibody-based subgroups in Malay SLE patients.Methods We studied 239 Malay patients fulfilling clinical SLE criteria. Serum samples were tested for 21 SLE-associated autoantibodies using the immunoblot and ELISA methods. Sociodemographic, lifestyle, clinical, and treatment data were collected systematically using a structured form. Subgroups were identified through unsupervised clustering, by applying the partitioning around medoids (PAM) algorithm to a Gower dissimilarity matrix constructed from 21 autoantibody positivity. Autoantibody feature importance was assessed with a random forest classifier. Associations with disease activity (SLEDAI-2K), clinical manifestations, and treatment were examined using logistic regression.Results Unsupervised clustering analysis identified four distinct subgroups: Subgroup 1 (41.4%) characterized by anti-nRNP/Sm IgM (55.6%); Subgroup 2 (26.8%) by anti-SSA/Ro60 IgG (85.9%) and anti-Ro52 IgG (75.6%); Subgroup 3 (12.1%) by anti-nucleosome IgG (93.1%), anti-histone IgG (93.1%), and anti-nRNP/Sm (86.2%); and Subgroup 4 (19.7%) was negative for the tested autoantibodies ( figure 1). Disease activity (SLEDAI-2K) was significantly higher in Subgroups 2 (Padj=0.02) and 3 (Padj<0.001) compared to Subgroup 4, while Subgroup 1 showed lower activity than Subgroup 4 (Padj=0.01). Subgroup 3 was strongly associated with mucocutaneous manifestations (OR 10.8, 95% CI 2.8–56.3) and renal involvement (OR 8.3, 95% CI 1.1–171.0). Treatment associations showed Subgroup 3 was linked to glucocorticoid use (OR 6.57, 95% CI 2.23–22.59) and methotrexate (OR 13.17, 95% CI 2.12–225.82), while Subgroup 2 was associated with glucocorticoids (OR 2.20, 95% CI 1.01–4.86) and azathioprine (OR 2.52, 95% CI 1.05–6.46). No associations were observed with hydroxychloroquine use.Abstract PO:02:032 Figure 1Conclusions Autoantibody-defined subgroups in Malay SLE patients demonstrated distinct clinical characteristics and treatment patterns. Subgroups 2 (anti-SSA/Ro60) and 3 (anti-nucleosome, anti-histone, anti-nRNP/Sm) were associated with higher disease activity and greater use of immunosuppressants. These findings support the utility of autoantibody profiling for patient stratification and management in diverse populations.",
  "authors": [
    {
      "affiliations": [
        "Sector Biostatistics and Data Repository, Office of NIH Manager, National Institutes of Health, Ministry of Health, Selangor, Malaysia",
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Lay-Kim Tan"
    },
    {
      "affiliations": [
        "Department of Medicine, University Malaya, Kuala Lumpur, Malaysia"
      ],
      "name": "Fariz Yahya"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden",
        "Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Lina Marcela Diaz-Gallo"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Elisabet Svenungsson"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden",
        "Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Ana Cristina Gonzalez-Sanchez"
    },
    {
      "affiliations": [
        "Bacteriology Unit, Infectious Disease Research Centre, Institute for Medical Research, National Institutes of Health, Mi, Selangor, Malaysia"
      ],
      "name": "Xue-Ting Tan"
    },
    {
      "affiliations": [
        "Department of Medicine, Selayang Hospital, Ministry of Health, Selangor, Malaysia"
      ],
      "name": "Ravathy Nasadurai"
    },
    {
      "affiliations": [
        "Department of Medicine, Selayang Hospital, Ministry of Health, Selangor, Malaysia"
      ],
      "name": "Habibah Mohd-Yusoof"
    },
    {
      "affiliations": [
        "Department of Medicine, Selayang Hospital, Ministry of Health, Selangor, Malaysia"
      ],
      "name": "Mollyza Mohd Zain"
    },
    {
      "affiliations": [
        "Department of Medicine, Selayang Hospital, Ministry of Health, Selangor, Malaysia"
      ],
      "name": "Malek Faris Riza Feisal Jeffrizal"
    },
    {
      "affiliations": [
        "Department of Medicine, Selayang Hospital, Ministry of Health, Selangor, Malaysia"
      ],
      "name": "Say-Lee Pok"
    },
    {
      "affiliations": [
        "Department of Medicine, Selayang Hospital, Ministry of Health, Selangor, Malaysia"
      ],
      "name": "Norliza Zainudin"
    },
    {
      "affiliations": [
        "Department of Medicine, Selayang Hospital, Ministry of Health, Selangor, Malaysia"
      ],
      "name": "Shereen Su-Yin Ch’ng"
    }
  ],
  "title": "PO:02:032 Defining systemic lupus erythematosus by autoantibody subgroups: clinical correlates and therapeutic insights",
  "uid": "bad77778-6141-5db0-bc57-c6b8c3cbab99"
}