{
  "abstract": "Introduction Gastrointestinal involvement is a major contributor to disease burden in systemic sclerosis (SSc). Small bowel dysmotility manifests with complications such as malnutrition, bacterial overgrowth, and, in severe cases, chronic intestinal pseudo-obstruction. The pathophysiology of small bowel dysmotility in SSc remains incompletely understood. Objective assessment of motor patterns and their correlation with immunopathological markers may improve disease stratification and understanding of biological pathways underlying SSc-GI mechanisms.Material and Methods Prospective study evaluating small bowel involvement in SSc patients between January 2018 and July 2025. Motility was measured using a high-resolution manometry catheter inserted into the proximal jejunum. Tracings were analyzed according to established criteria and categorized as normal or abnormal (myopathic or neuropathic). Clinical characteristics and other GI parameters (esophageal manometry and gastric emptying scintigraphy) were compared between groups. To explore associations between motility patterns and autoantibodies binding the ENS, serum samples were incubated with freshly isolated longitudinal muscle–myenteric plexus (LM-MP) from Wnt1-cre:tdTomato neural crest-fate-mapping mice. Immunostaining patterns were assessed and correlated with motility status.Results We included forty patients. Of these, 26(65%) demonstrated objective small bowel dysmotility, characterized by either a myopathic pattern(n=15; 57.7%) or a neuropathic pattern(n=11; 42.3%). The remaining 14 patients(35%) exhibited motility patterns within normal limits. Diffuse cutaneous SSc was more prevalent among patients with small bowel dysmotility compared to those with normal motility(34.6% vs 14.3%; p=0.170). Ro/SSA antibody positivity was observed exclusively in the dysmotility group(19.2% vs 0%; p=0.079). No significant associations were found between small bowel dysmotility and esophageal involvement(76.9% vs 64.3%; p=0.345) or gastric emptying(mean retention at 4-hours: 14.4±15.9% vs 12.6±13.3%; p=0.699). All patients exhibited positive immunostaining of the myenteric plexus(100%). However, intravillous staining was significantly more frequent in patients with small bowel dysmotility (96.2% vs 71.4%; p=0.024), and diffuse longitudinal muscle and myenteric plexus staining showed a trend (65.4% vs 35.7%; p=0.072). No significant differences were observed in mucosal or submucosal staining patterns.Conclusions In this prospective cohort, small bowel dysmotility was present in two-thirds of individuals and was associated with distinct immunohistochemical patterns, particularly in the myenteric and intravillous layers of the gut. These findings support the hypothesis that autoantibody-mediated targeting of neuromuscular structures may contribute to the pathogenesis of GI motor dysfunction in SSc. Further investigation of these immunologic mechanisms may offer insights into disease severity and guide the development of targeted therapeutic strategies",
  "authors": [
    {
      "affiliations": [
        "Digestive System Research Unit, Barcelona, Spain"
      ],
      "name": "Luis Alcala"
    },
    {
      "affiliations": [
        "Internal Medicine department, Barcelona, Spain"
      ],
      "name": "Alfredo Guillen-del-Castillo"
    },
    {
      "affiliations": [
        "Digestive System Research Unit, Barcelona, Spain"
      ],
      "name": "Francisco Felix-Tellez"
    },
    {
      "affiliations": [
        "Internal Medicine department, Barcelona, Spain"
      ],
      "name": "Claudia Codina"
    },
    {
      "affiliations": [
        "Digestive System Research Unit, Barcelona, Spain"
      ],
      "name": "Carolina Malagelada"
    },
    {
      "affiliations": [
        "Internal Medicine department, Barcelona, Spain"
      ],
      "name": "Carmen P Simeon-Aznar"
    },
    {
      "affiliations": [
        "Internal Medicine department, Barcelona, Spain"
      ],
      "name": "Laura Triginer"
    },
    {
      "affiliations": [
        "Immunology department, Barcelona, Spain"
      ],
      "name": "Janire Perurena"
    },
    {
      "affiliations": [
        "Immunology department, Barcelona, Spain"
      ],
      "name": "Laura Viñas"
    },
    {
      "affiliations": [
        "Immunology department, Barcelona, Spain"
      ],
      "name": "Maite Sanz"
    },
    {
      "affiliations": [
        "Division of Medical Sciences, Harvard Medical School, Boston, USA",
        "Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, USA"
      ],
      "name": "Subhash Kulkarni"
    },
    {
      "affiliations": [
        "UTHealth Houston, Department of Medicine, Division of Rheumatology, Husto, USA"
      ],
      "name": "Zsuzsanna McMahan"
    }
  ],
  "title": "P.184 Autoantibodies targeting the cellular subsets in the ENS correlate with small bowel dysmotility patterns in patients with systemic sclerosis",
  "uid": "6d444b5e-4165-5a75-b7f5-aeab2b510b5c"
}