{
  "abstract": "Objectives\n\nGiant cell arteritis (GCA) is characterized by chronic large-vessel inflammation and remodelling. Within affected arteries, especially in aorta, organized B cell clusters are mainly localized in adventitia, where fibroblasts represent the dominant stromal population. This study aims to investigate fibroblast heterogeneity within these clusters and B cell-fibroblast interactions in vitro as possible contributors to disease chronicity in GCA.Methods\n\nFibroblast phenotypes in CD20+ B cell clusters in GCA and atherosclerotic aortic tissues were characterized using immunohistochemistry for fibroblast markers (CD90, podoplanin [PDPN], fibroblast activation protein [FAP], CD248, α-smooth muscle actin [α-SMA]) and cytokine expression (IL-6, GM-CSF, B-cell activating factor [BAFF]). In vitro, peripheral blood B cells from treatment-naïve GCA patients and healthy donors were stimulated and cocultured with human aortic adventitial fibroblasts (HAoAFs) using either direct cell coculture or transwell systems. To identify relevant molecular pathways for B cell-fibroblast interaction, HAoAFs were pre-treated with infliximab, tocilizumab, baricitinib or upadacitinib, followed by exposure to activated B cell conditioned medium. Protein secretion was assessed by ELISA, Luminex and Olink; mRNA expression was determined by qPCR.Results\n\nCD90+PDPN+ immunofibroblasts mainly localized centrally, whereas CD90+FAP+ and CD90+CD248+ fibroblasts mostly located at the border of the clusters. Fibroblasts in or around clusters co-expressed IL-6, GM-CSF and BAFF. In vitro, HAoAFs cocultured with activated B cells or supernatants thereof upregulated IL-6, GM-CSF, PDPN and FAP mRNA, and actively secreted IL-6, GM-CSF and BAFF, while type I collagen expression was suppressed. Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibition abrogated these pro-inflammatory effects, whereas TNF-α and IL-6 receptor blockade did not.Conclusion\n\nActivated B cells drive fibroblasts toward a pro-inflammatory phenotype, potentially sustaining chronic inflammation and disease progression in GCA. JAK-STAT signalling appears central to this effect, highlighting its therapeutic potency at the vascular level in GCA.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.",
    "Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.",
    "Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, UAE."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shuang Xu",
      "orcid": "0000-0001-8071-2830"
    },
    {
      "affs": [
        0
      ],
      "name": "William F Jiemy"
    },
    {
      "affs": [
        1
      ],
      "name": "Nanthicha Inrueangsri"
    },
    {
      "affs": [
        0
      ],
      "name": "YouBeen Ko"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Wayel H Abdulahad",
      "orcid": "0000-0003-3109-4487"
    },
    {
      "affs": [
        0
      ],
      "name": "Ellen Verschoor"
    },
    {
      "affs": [
        0
      ],
      "name": "Yannick van Sleen",
      "orcid": "0000-0002-7382-8322"
    },
    {
      "affs": [
        0
      ],
      "name": "Jacoba C Graver"
    },
    {
      "affs": [
        0
      ],
      "name": "Kornelis S M van der Geest",
      "orcid": "0000-0003-2798-6765"
    },
    {
      "affs": [
        0
      ],
      "name": "Gwenny M Verstappen"
    },
    {
      "affs": [
        0
      ],
      "name": "Elisabeth Brouwer",
      "orcid": "0000-0002-5652-4423"
    },
    {
      "affs": [
        1
      ],
      "name": "Peter Heeringa",
      "orcid": "0000-0001-8684-763X"
    },
    {
      "affs": [
        0
      ],
      "name": "Annemieke M H Boots"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Sandovici",
      "orcid": "0000-0002-4809-0653"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ff62vb23svk1m.bib",
  "cited_by": 0,
  "doi": "10.1093/rheumatology/keag563",
  "fulltext_url": "https://europepmc.org/articles/PMC13707385",
  "id": "ff62vb23svk1m",
  "issns": [
    "1462-0324",
    "1462-0332"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897993",
  "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": [
    [
      "openalex",
      "2740|Vasculitis and related conditions"
    ]
  ],
  "openalex": "W7223013733",
  "pdf_url": "https://europepmc.org/articles/PMC13707385?pdf=render",
  "pmcid": "PMC13707385",
  "pmid": "42897993",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ff62vb23svk1m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42897993",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897993"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Vasculitis and related conditions",
      "subfield": "general"
    }
  ],
  "title": "Activated B cells steer fibroblasts towards a proinflammatory phenotype in giant cell arteritis.",
  "title_text": "Activated B cells steer fibroblasts towards a proinflammatory phenotype in giant cell arteritis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/ff62vb23svk1m",
  "venue": "Rheumatology (Oxford, England)",
  "versions": []
}