{
  "abstract": "Introduction Systemic sclerosis (SSc) is characterized by three major mechanisms: immune dysregulation, fibrosis, and vasculopathy. Gastrointestinal (GI) involvement affects 50-90% of patients and is associated with significant morbidity and mortality, while therapeutic options remain limited. Most studies on the pathophysiology of GI involvement have highlighted vascular and neurogenic mechanisms in digestive dysfunction. By contrast, the contribution of immune dysregulation has been underexplored, despite its recognized role in other visceral manifestations of SSc. Innate lymphoid cells (ILCs), key players of innate immunity, contribute to host defense and tissue homeostasis at barrier sites such as the gut.We hypothesized that innate immune responses, particularly ILCs, may be involved in GI manifestations of SSc. The main objective of this study was to characterize both quantitatively and qualitatively immune cell subsets, including ILCs, in blood and intestinal samples from patients with SSc.Material and Methods GI involvement in patients with SSc was assessed using the UCLA GIT 2.0 questionnaire. ILCs from SSc patients and healthy donors (HD) were identified from blood using multiparametric flow cytometry (2 million events recorded). Flow cytometry data were analyzed with FlowJo 10.7.1, and statistical analyses were performed with GraphPad Prism 10. Fresh GI biopsies were obtained during colonoscopy. Cytological and histological analyses (IHC, IF, Sirius Red) were performed. Histological slides were digitized using a VS200 scanner and analyzed with QuPath software.Results The percentage of blood ILCs among CD45+ cells was significantly lower in SSc patients (n=17) compared with HD (n=14) ( figure 1) respectively 0.009 (0–0.021) vs. 0.026 (0.015–0.068). Subsets ILC1, ILC2, and ILC3 were also significantly reduced in the blood of SSc patients versus HD respectively (p<0.002) ILC1: 0.0016 (0–0.0068) vs. 0.0053 (0.0024–0.014), ILC2: 0.0036 (0–0.014) vs. 0.011 (0.0031–0.033), ILC3: 0.0011 (0–0.0049) vs. 0.0061 (0.002–0.02). No significant correlation was observed between circulating ILC frequency and UCLA GIT 2.0 scores.Preliminary data indicate an increased submucosal area positive for fibrosis associated Sirius Red staining in SSc patients with lower GI involvement, compared with control (p=0.02). CD3+ lymphocytes appeared predominant on histological samples.Conclusions Circulating ILCs were significantly reduced in SSc patients compared with HD suggesting redistribution or migration toward mucosal sites. Preliminary histological findings suggested enhanced fibrosis in colonic SSc biopsy. Further cytological and histological analyses are ongoing to better define the immune landscape of SSc gut involvement and its potential as a therapeutic target.Abstract P.063 Figure 1",
  "authors": [
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Louis Bébéar"
    },
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Alexis Jean"
    },
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Pauline Riviere"
    },
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Damien Brisou"
    },
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Isabelle Douchet"
    },
    {
      "affiliations": [
        "University of Bordeaux, Histopathologie CNRS UMS 3427 / US 05, Bordeaux, France"
      ],
      "name": "Nathalie Senant"
    },
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Edouard Forcade"
    },
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Estibaliz Lazaro"
    },
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Christophe Richez"
    },
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Cécile Bordes"
    },
    {
      "affiliations": [
        "University of Bordeaux, ImmunoConcept CNRS UMR5164, Bordeaux, France"
      ],
      "name": "Marie-Elise Truchetet"
    }
  ],
  "title": "P.063 Innate lymphoid cell alterations and enhanced intestinal fibrosis in systemic sclerosis: evidence for an immune contribution to gastrointestinal involvement",
  "uid": "fceed778-72a8-5c49-b590-65d5fca5d865"
}