{
  "abstract": "OBJECTIVES: The X chromosome-linked Toll-like receptor (TLR)7 gene contributes to type I interferon (IFN) expression in systemic lupus erythematosus (SLE). Recently, ultra-rare variants in TLR7 have been linked with Mendelian forms of SLE. METHODS: Targeted new-generation sequencing was used to identify TLR7 coding variants in 319 patients with juvenile-onset (j)SLE from the UK. Functional studies investigated molecular impacts associated with a previoulsy unreported gene variant in TLR7. RESULTS: The previously unreported private TLR7 coding variant p.Glu834* (heterozygous), introducing a stop codon, was identified in a female patient with jSLE with multisystemic disease and a family history of lupus-like autoimmunity and premature deaths. The patient was born preterm and exhibited neurodevelopmental delay and severe neuropsychiatric involvement. On the molecular level, TLR7 p.Glu834* is associated with sustained interaction with the UNC93B1 chaperone, allowing endolysosomal integration and noncanonical dimerisation with TLR8, resulting in enhanced proinflammatory cytokine expression following TLR7/8 engagement. In vitro observations were mirrored by an elevated IFN signature in peripheral blood cells from the patient. Molecular modelling indicated that formation of the TLR8:TLR7 p.Glu834* heterodimer is possible because of the shape complementarity of TLR7 and TLR8, and a more favourable interaction at the dimer interface for the TLR8:TLR7 p.Glu834* as compared with the endogenous TLR8:TLR8 dimer. CONCLUSIONS: Observations suggest that the private truncating TLR7 p.Glu834* variant associates with SLE-like clinical pictures through coupling with TLR8. Findings expand the list of SLE-associated disease mechanisms and support genetic risk stratification and consideration of TLR and/or IFN-targeted treatments.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 32,
  "authors": [
    {
      "name": "Yves Renaudineau"
    },
    {
      "name": "Jenny Hawkes"
    },
    {
      "name": "Katarzyna Mizgalska"
    },
    {
      "name": "Valentina Natoli"
    },
    {
      "name": "Joni Roachdown"
    },
    {
      "name": "Lola Cusin"
    },
    {
      "name": "Francesca Sposito"
    },
    {
      "name": "Ethan Sen"
    },
    {
      "name": "Alison Kinder"
    },
    {
      "name": "Mathieu Fusaro"
    },
    {
      "name": "Wesley Brooks"
    },
    {
      "name": "Wayne Guida"
    },
    {
      "name": "Aleksandra Karolak"
    },
    {
      "name": "Amandine Charras"
    },
    {
      "name": "Michael Beresford"
    },
    {
      "name": "Christian Hedrich"
    },
    {
      "name": "Carla Roberts"
    },
    {
      "name": "Eslam Al-Abadi"
    },
    {
      "name": "Kate Armon"
    },
    {
      "name": "Kathryn Bailey"
    },
    {
      "name": "Coziana Ciurtin"
    },
    {
      "name": "Janet Gardner-Medwin"
    },
    {
      "name": "Kirsty Haslam"
    },
    {
      "name": "Daniel Hawley"
    },
    {
      "name": "Alice Leahy"
    },
    {
      "name": "Valentina Leone"
    },
    {
      "name": "Flora Mcerlane"
    },
    {
      "name": "Gita Modgil"
    },
    {
      "name": "Clarissa Pilkington"
    },
    {
      "name": "Athimalaipet Ramanan"
    },
    {
      "name": "Satyapal Rangaraj"
    },
    {
      "name": "Phil Riley"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b8b6gsn8gm6fj.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ard.2026.07.024",
  "fulltext_url": null,
  "id": "b8b6gsn8gm6fj",
  "issns": [
    "0003-4967",
    "1468-2060"
  ],
  "landing_url": "https://hal.science/hal-05757155v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2745|Systemic Lupus Erythematosus Research"
    ]
  ],
  "openalex": "W7203975646",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "BMJ Publishing Group",
  "ris": "https://research.draconitic.com/paper/b8b6gsn8gm6fj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "hal-05757155",
      "source": "hal",
      "url": "https://hal.science/hal-05757155v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:0.sdv",
      "subfield": "general"
    }
  ],
  "title": "The private truncating Toll-like receptor 7 p.Glu834* variant associates with juvenile-onset systemic lupus erythematosus and pathological cytokine expression in vitro",
  "title_text": "The private truncating Toll-like receptor 7 p.Glu834* variant associates with juvenile-onset systemic lupus erythematosus and pathological cytokine expression in vitro",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/b8b6gsn8gm6fj",
  "venue": "Annals of the Rheumatic Diseases",
  "versions": []
}