{
  "abstract": "ObjectivesHomeostatic natural autoantibodies (nAAbs) are proposed regulators of inflammation and autoimmunity, studied mainly as natural IgM. Whether pathological autoantibody (pAAb) expansion in systemic lupus erythematosus (SLE)-associated serology is mirrored by isotype-divergent nAAb changes has rarely been examined.MethodspAAb positivity and co-positivity ratios (exact 95% confidence intervals) and intersection (UpSet) analyses were derived from a regional diagnostic cohort (Southern Transdanubia, Hungary, 2014–2024; 128,847 enzyme-linked immunosorbent assay (ELISA) results, 73,747 pseudonymised patients). The dominant patterns defined anti-double-stranded DNA (a-dsDNA)/anti-nucleosome-, anti-SSA/Ro- and anti-cardiolipin/β2-glycoprotein I (a-CL/β2GPI)-dominant and co-positive groups, each verified against serological follow-up. In 110 residual sera, IgG and IgM nAAbs against citrate synthase (CS) and heat shock proteins (HSP) 60 and 70 were measured by ELISA and compared by Kruskal–Wallis and Dunn–Holm tests.ResultsOf a-dsDNA IgG-positive patients, 30.36% carried an additional disease-specific pAAb, along two largely separate axes, antiphospholipid (15.90%) and extractable nuclear antigen-associated (16.51%); anti-neutrophil cytoplasmic antibody co-positivity was rare (3.02%), and 42.01% showed a-nucleosome co-reactivity. a-CS IgM was reduced in every pAAb-positive group (all pHolm < 0.001), whereas increased a-CS, a-HSP60 and a-HSP70 IgG levels were confined to a-dsDNA/a-nucleosome-containing (chromatin-reactive) profiles (a-CS IgG, pHolm ≤ 0.012). These shifts were robust to sex-, age- and measurement-year adjustment.ConclusionIsotype-resolved nAAb profiling anchored in diagnostic serology revealed a counter-directional shift (IgM↓ across pAAb-positive groups, IgG↑ in chromatin-reactive profiles). These hypothesis-generating findings are consistent with impaired homeostatic IgM-mediated regulation and with class-switched IgG nAAb reactivity as a marker of B-cell activation, and warrant clinical and functional validation in prospective cohorts.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Dávid Szinger"
    },
    {
      "name": "Katalin Böröcz"
    },
    {
      "name": "Diána Simon"
    },
    {
      "name": "Alain Le Roux"
    },
    {
      "name": "Szabina Erdő-Bonyár"
    },
    {
      "name": "Nancy Zeineddine"
    },
    {
      "name": "Péter Németh"
    },
    {
      "name": "Timea Berki"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9qdbew1y4dtx6.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1936421",
  "fulltext_url": null,
  "id": "9qdbew1y4dtx6",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1936421",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/9qdbew1y4dtx6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.3389/fimmu.2026.1936421",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1936421"
    },
    {
      "first_seen": "2026-10-30T12:19:19Z",
      "native_id": "10.3389/fimmu.2026.1936421",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1936421/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Isotype-dependent shifts of natural autoantibody profiles in systemic lupus erythematosus-associated serological groups",
  "title_text": "Isotype-dependent shifts of natural autoantibody profiles in systemic lupus erythematosus-associated serological groups",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T00:20:56Z",
  "url": "https://research.draconitic.com/paper/9qdbew1y4dtx6",
  "venue": "Frontiers in Immunology",
  "versions": []
}