{
  "abstract": "Autoantibodies against type I IFNs can severely compromise antiviral defense, yet the mechanisms underlying their development remain elusive. Using high-throughput autoantigen profiling, we observed that a subgroup of severe COVID-19 patients exhibited strong binding to multiple type I IFNs. Integrated single-cell RNA and B cell receptor (BCR) sequencing with functional analysis identified B cell subsets/states enriched for IFN-α2-binding and -neutralizing antibodies in COVID-19. These findings were compared with those from patients with autoimmune polyendocrine syndrome type I, a rare genetic disease characterized by defective immune tolerance and persistent type I IFN autoimmunity. Competition surface plasmon resonance and AlphaFold 3 structural modeling identified three major functional epitope groups and seven predicted structural subclasses among neutralizing antibodies. Our results indicate that IFN-α2 autoreactivity is present in both naive and antigen-experienced B cell compartments, whereas functional IFN-neutralizing antibodies are predominantly associated with memory and atypical B cells, consistent with defective tolerance and affinity maturation-mediated selection of autoreactive B cell clones.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.",
    "Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University , Beijing, China.",
    "Institute for Research in Biomedicine, Università Della Svizzera Italiana , Bellinzona, Switzerland.",
    "Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.",
    "Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.",
    "Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.",
    "Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.",
    "Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, Italy.",
    "Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.",
    "Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 29,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rui Sun",
      "orcid": "0009-0007-2117-6696"
    },
    {
      "affs": [
        1
      ],
      "name": "Siyu Lin",
      "orcid": "0009-0007-4282-6790"
    },
    {
      "affs": [
        2
      ],
      "name": "Luca Simonelli",
      "orcid": "0000-0001-6331-7716"
    },
    {
      "affs": [
        3
      ],
      "name": "Benedikt Strunz",
      "orcid": "0000-0001-9974-6133"
    },
    {
      "affs": [
        4
      ],
      "name": "Anish Behere",
      "orcid": "0000-0002-2424-3475"
    },
    {
      "affs": [
        2
      ],
      "name": "Mattia Pedotti",
      "orcid": "0000-0003-1370-9505"
    },
    {
      "affs": [
        1
      ],
      "name": "Tian Xu",
      "orcid": "0009-0008-8710-8896"
    },
    {
      "affs": [
        0
      ],
      "name": "Fanglei Zuo",
      "orcid": "0000-0002-4545-1265"
    },
    {
      "affs": [
        0
      ],
      "name": "Likun Du",
      "orcid": "0000-0002-8448-2187"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Wan",
      "orcid": "0000-0002-4368-8672"
    },
    {
      "affs": [
        2
      ],
      "name": "Sara Lestani",
      "orcid": "0009-0000-9485-7838"
    },
    {
      "affs": [
        0
      ],
      "name": "Leire de Campos-Mata",
      "orcid": "0000-0003-1998-4014"
    },
    {
      "affs": [
        0
      ],
      "name": "Stelios Vlachiotis",
      "orcid": "0009-0009-0630-4316"
    },
    {
      "affs": [
        0
      ],
      "name": "Dorottya Kalmár",
      "orcid": "0009-0000-7949-9980"
    },
    {
      "name": "Karolinska KI/K COVID-19 Study Group"
    },
    {
      "affs": [
        3,
        5
      ],
      "name": "Kristoffer Strålin",
      "orcid": "0000-0002-8801-3169"
    },
    {
      "affs": [
        3,
        5
      ],
      "name": "Soo Aleman",
      "orcid": "0000-0003-0461-4870"
    },
    {
      "affs": [
        3
      ],
      "name": "Hans-Gustaf Ljunggren",
      "orcid": "0000-0003-0908-7387"
    },
    {
      "affs": [
        6
      ],
      "name": "Antonio Piralla",
      "orcid": "0000-0002-6062-2579"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Fausto Baldanti",
      "orcid": "0000-0002-3358-8969"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Olle Kämpe",
      "orcid": "0000-0001-6091-9914"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Sophie Bensing",
      "orcid": "0000-0002-9193-2860"
    },
    {
      "affs": [
        0
      ],
      "name": "Lennart Hammarström",
      "orcid": "0000-0002-8635-9609"
    },
    {
      "affs": [
        4
      ],
      "name": "Nils Landegren",
      "orcid": "0000-0002-6163-9540"
    },
    {
      "affs": [
        1
      ],
      "name": "Zexian Zeng",
      "orcid": "0000-0002-3905-3244"
    },
    {
      "affs": [
        3
      ],
      "name": "Niklas K Björkström",
      "orcid": "0000-0002-0967-076X"
    },
    {
      "affs": [
        2
      ],
      "name": "Luca Varani",
      "orcid": "0000-0002-0963-0987"
    },
    {
      "affs": [
        0
      ],
      "name": "Harold Marcotte",
      "orcid": "0000-0002-7168-349X"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiang Pan-Hammarström",
      "orcid": "0000-0003-1990-8804"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bnq3e1qbvqtmx.bib",
  "cited_by": 0,
  "doi": "10.1084/jem.20260268",
  "fulltext_url": "https://europepmc.org/articles/PMC13729907",
  "id": "bnq3e1qbvqtmx",
  "issns": [
    "0022-1007",
    "1540-9538"
  ],
  "landing_url": "https://europepmc.org/article/MED/42975591",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "heading",
      "Autoimmunity"
    ],
    [
      "heading",
      "Infectious Disease and Host Defense"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7225139524",
  "pdf_url": "https://europepmc.org/articles/PMC13729907?pdf=render",
  "pmcid": "PMC13729907",
  "pmid": "42975591",
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bnq3e1qbvqtmx.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:47Z",
      "native_id": "MED:42975591",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42975591"
    },
    {
      "first_seen": "2026-11-07T12:22:38Z",
      "native_id": "PMC13729907",
      "source": "pmc",
      "url": "https://doi.org/10.1084/jem.20260268"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Cellular origin and characterization of autoantibodies against type I IFNs in COVID-19 and APS-1.",
  "title_text": "Cellular origin and characterization of autoantibodies against type I IFNs in COVID-19 and APS-1.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:38Z",
  "url": "https://research.draconitic.com/paper/bnq3e1qbvqtmx",
  "venue": "The Journal of experimental medicine",
  "versions": []
}