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Introduction CD19-targeting CAR T cells showed remarkable improvements in autoimmune diseases and promising data showing safety and clinical efficacy in patients with diffuse Systemic Sclerosis (SSc) have been reported [Auth et al., 2025]. However, the impact of the therapy on gastrointestinal (GI) symptoms has not been studied yet. Here we analyze development of GI symptoms in eight SSc patients after receiving CD19-targeting CAR T cell therapy.Material and Methods CD19-targeting CAR T cells were acquired as previously described [Müller et al., 2024]. Patients received the therapy at the University hospital Erlangen as part of the CASTLE study [Schett et al., 2024]. Immunosuppression was stopped before CAR T cell infusion and the therapy was performed upon lymphodepletion with fludarabine (25 mg/m2 on days -5, -4, -3) and cyclophosphamide (1g/m2 on day -3) as single infusion with 1x10^6 CAR T cells/kg. Patients filled out the UCLA Scleroderma Clinical Trial Consortium GIT 2.0 questionnaire at baseline and regularly throughout the follow up period. Changes in questionnaire scores were evaluated according to the minimally important differences (MID) reported [Khanna et al., 2011].Results Eight patients with progressive dcSSc received CD19-targeting CAR T cell therapy, four females and four males with a median age of 31.5 years (IQR 26.75 – 37.75). The median disease duration at baseline was 33 months (IQR 21 – 48.5). All patients showed signs of GI involvement at baseline, mostly esophageal dysmotility, and have received at least two state-of-the-art treatments before being scheduled for CAR T therapy. Looking at the UCLA SCTC GIT 2.0 questionnaires, total scores improved by a median of -0.209 after 3 months and -0.186 after 6 months, therefore showing a significant clinical improvement by meeting the MID for ‘somewhat better’ at the 3 months-time point (MID = -0.20). Analyzing the score changes in the different questionnaire subcategories, an improvement especially of distension/bloating with scores above MID values was reported after 3 months. At 6 months, MID values were met for distension/bloating, social functioning and constipation, indicating a significant clinical improvement in the abovementioned categories.Conclusions These data show for the first time that CD19-targeting CAR T cell therapy can lead to improvement of GI symptoms. Longer follow up data and comparisons with state-of-the-art treatments are needed.