{
  "abstract": "Introduction Patient feedback shows that gastrointestinal (GI) complications are frequent and disabling manifestations of systemic sclerosis (SSc). Unlike the skin, GI disease does not respond to immunosuppression and generally worsens with time. We have previously analysed gastric tissue from SSc patients and HC, and showed significant differences in fibroblast subsets, expansion of the CD8+ T cell compartment, and significant reduction in plasma cells. Here we utilise single-cell technologies to understand disease pathogenesis in the colon.Material and Methods Colonic biopsies were obtained from 4 SSc patients and 4 healthy controls (HC). Single-cell RNA sequencing (scRNAseq) and spatial transcriptomics were performed on whole biopsies using 10X Genomics Chromium workflow and 10X Xenium. Data were analysed using scanpy, scvi-tools, and squidpy.Results After filtering, 27,274 cells were analysed using scRNAseq. Within the immune cell compartment of the colon tissue, there was an increase in IgA plasma cells, and memory B cells in SSc compared to HC.The most abundant fibroblast cluster in the colon was a proinflammatory-like fibroblast (PDGFRA+). There was no significant difference in abundance between SSc and HC in this cluster, but gene-set enrichment revealed downregulation of the extracellular matrix organisation, and collagen fibril organisation biological process pathways.Comparison across disease and tissue types highlighted even in health, there were fewer fibroblasts, but more abundant B cells in the colon compared to gastric tissue, suggesting that the pathology may not be uniform across all GI tissue types in SSc. There was also a reduction in cd8+ t cells in ssc colon tissue, unlike in the gastric tissue, where there is a significant expansion of the cd8+ t cell cluster (figure 1).Spatial transcriptomic analysis showed the macrophage-fibroblast niche plays a significant role in SSc compared to HC. There was a profound increase in PDGFRA+ fibroblasts and proinflammatory macrophages (CD206+/MERTK+) within the lamina propria surrounding the crypts of SSc tissue, whereas both these fibroblasts and macrophages were barely present in the HC tissue.Conclusions Using single-cell analysis, we show significant differences in cell abundance between SSc and HC in the colon, that also differ between gastric and colonic tissue. Thus, cellular pathology is not uniform throughout the GI tract. Notably, although scRNAseq confirms similar abundance of proinflammatory fibroblasts between SSc and HC, spatial transcriptomics suggests location-specific differences in interaction between fibroblasts and macrophages that may drive GI fibrosis.Abstract P.034 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Kennedy Institute of Rheumatology, Oxford, United Kingdom"
      ],
      "name": "Kristina Clark"
    },
    {
      "affiliations": [
        "Kennedy Institute of Rheumatology, Oxford, United Kingdom"
      ],
      "name": "Moustafa Attar"
    },
    {
      "affiliations": [
        "Translational Gastrointestinal Unit, Oxford, United Kingdom"
      ],
      "name": "Matthias Friedrich"
    },
    {
      "affiliations": [
        "Royal Free Hospital NHS Foundation Trust, London, United Kingdom"
      ],
      "name": "Charles Murray"
    },
    {
      "affiliations": [
        "Kennedy Institute of Rheumatology, Oxford, United Kingdom"
      ],
      "name": "Alexander Clarke"
    },
    {
      "affiliations": [
        "University College London, London, United Kingdom"
      ],
      "name": "Christopher Denton"
    }
  ],
  "title": "P.034 Navigating the single-cell landscape of colonic disease in systemic sclerosis",
  "uid": "feb0850b-5970-5c26-83fd-afe87c3991be"
}