{
  "id": 18562363,
  "title": "Preferential Isoform Usage and Isoform Switching in Systemic Lupus Erythematosus Patients with Distinct Autoantibody Profile",
  "url": "https://urgent.news/2026/11/06/preferential-isoform-usage-and-isoform-switching-in-systemic-lupus",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-11-06T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.11.05.764679v1?rss=1"
  },
  "original_language": "en",
  "account": "Recent advancements in RNA sequencing have illuminated the complex molecular nuances of systemic lupus erythematosus (SLE); yet, many previous investigations have primarily concentrated on differential gene expression, which fails to capture the intricacies of the transcriptome. Isoforms, formed through alternative splicing and polyadenylation from a single gene, can contribute to autoimmune pathology via their production of non-canonical variants with potential autoantigenic characteristics. To delve into this underexplored facet, researchers examined differential isoform usage (DIU) and major isoform switching (MIS) in SLE categories categorized by autoantibody signatures: anti-dsDNA+, anti-ENA+, and anti-dsDNA+ENA+. Subgroup-specific DIU and MIS events were identified to be enriched in RNA-binding and transcription-related operations. In the anti-dsDNA+ cohort, the T-cell receptor adaptor GRAP2 exhibited isoform switching, coupled with a surge in a non-coding retained-intron transcript. Anti-ENA+ patients showcased IGHM transitioning from a membrane-bound to a secretory form, aligning with an antibody-secreting cell profile; NACA, a recognized IgE autoantigen, experienced isoform switching; and BRI3, implicated in TNF-α-induced cell death, migrated towards its protein-coding transcript. In the anti-dsDNA+ENA+ cohort, TNFAIP2, a TNF-α induced gene, displayed isoform redistribution, accompanied by the loss of a uORF-containing transcript. These insights underscore isoform regulation as a unique, subgroup-specific, and functionally significant dimension of transcriptomic dysregulation in SLE.",
  "summary": "RNA sequencing has advanced our understanding of molecular heterogeneity in systemic lupus erythematosus (SLE), yet most studies have focused on differential gene expression (DGE), which overlooks transcript-level complexity. Alternative splicing and polyadenylation generate multiple isoforms from a single gene, and their dysregulation may contribute to autoimmune pathogenesis, including through…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 2,
    "also_reported_by": [
      {
        "outlet": "Medical Xpress",
        "title": "Postoperative complications elevated for patients with systemic lupus erythematosus",
        "url": "https://urgent.news/2026/11/03/postoperative-complications-elevated-for-patients-with-systemic-lupus",
        "published": "2026-11-03T18:40:08.000Z"
      }
    ]
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}