{
  "abstract": "Introduction The IL-17 cytokine family comprises of six members (IL-17A–F) with diverse functions in immune regulation, inflammation, and tissue homeostasis. Among these, IL-17A and IL-17F have been most studied, with evidence linking IL-17A to pathogenic inflammation, fibroblast activation, and vascular dysfunction in systemic sclerosis (SSc). Elevated IL-17A levels have been detected in patient blood and skin, and experimental models suggest it contributes to both immune cell recruitment and fibroblast-driven tissue remodelling. In contrast, IL-17B and IL-17D remain poorly understood, though emerging studies indicate they may exert context-dependent effects on tissue inflammation, stromal activation, and fibrosis. Understanding their presence and function in SSc could reveal novel pathogenic mechanisms and therapeutic opportunities. Here, we sought to generate specific antibodies against IL-17B and IL-17D as tools to probe their expression in SSc pathogenesis.Material and Methods In order to explore IL-17 family expression in SSc, high-affinity antibodies against human IL-17B and IL-17D were developed using recombinant FC-fusion proteins. Rabbits were immunised with recombinant proteins and candidate antibodies were selected via the UCB antibody screening platform using high-throughput automation and the fluorescent foci picking methods to isolate antigen-specific B cells. Resultant antibodies were tested for binding specificity across protein sources (mammalian and non-mammalian) and to formalin-fixed proteins to mimic immunohistochemical (IHC) compatible conditions.Results IL-17B and IL-17D constructs were successfully expressed and purified from mammalian systems, generating a toolbox of reagents for downstream assays. E. coli-derived proteins were used as immunogens for antibody discovery, while a flow cytometry–based screen employing mammalian proteins identified multiple antigen-specific antibodies with IHC potential. Single B cell isolation and sequencing confirmed diverse IL-17B and D antibody repertoire, including several dominant clonotypes recognising distinct epitopes.Conclusions This project established effective pipelines for producing IL-17B and IL-17D reagents and antibodies. The identification of diverse clonotypes provides a strong basis for selecting IHC and candidates for expression studies. Future work will focus on mining these repertoires to define lead IL-17B and IL-17D antibodies with the potential to serve as critical tools for elucidating their roles in systemic sclerosis.",
  "authors": [
    {
      "affiliations": [
        "University College of London, London, United Kingdom"
      ],
      "name": "Avneet Kaur Manghera"
    },
    {
      "affiliations": [
        "UCB Pharma, Slough, United Kingdom"
      ],
      "name": "Alastair Lawson"
    },
    {
      "affiliations": [
        "University College of London, London, United Kingdom"
      ],
      "name": "Voon Ong"
    },
    {
      "affiliations": [
        "University College of London, London, United Kingdom"
      ],
      "name": "David Abrahams"
    }
  ],
  "title": "P.024 Generating IL-17B and IL-17D specific antibodies to investigate their potential role in driving systemic sclerosis",
  "uid": "a24e5fa9-5614-5d19-857c-3ff9c02745c6"
}