POS0867 ALTERATION OF DUODENAL HISTOLOGY IN SYSTEMIC SCLEROSIS PATIENTS AFTER FECAL MICROBIOTA TRANSPLANTATION

Background: Systemic sclerosis (SSc) is a complex autoimmune, multi-organ disease with gastro-intestinal tract (GIT) involvement significantly contributing to comorbidity. While understanding of mechanisms behind SSc-related GIT incomplete, recent work shows that altered gut microbiota (dysbiosis) present in many patients and associates specific symptoms. Intending improve dysbiosis, we set up the controlled ReSScue pilot trial, where fecal transplantation (FMT) was conducted by duodenal infusions Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) or placebo. The results indicated FMT ACHIM induced short-term improvement on patient reported symptoms, as evaluated validated UCLA score (1). Duodenal biopsies were taken before after assess potential effects small intestinal mucosa. Objectives: Assessment histology symptoms compared Methods: In this explorative study, assessed collected prior first (week 0), second 2) at study end 16) from trial who either received (n=5) placebo (n=4). To examine mucosa, performed immunohistochemistry (IHC) staining paraffin-embedded tissue samples using following markers: Sirius red (SIR) for collagen fibers monoclonal antibodies against gp38 (podoplanin, marker lymphatic vessels fibroblasts), CD38 (as preliminary adaptive immune cells) CD64 innate cells). We determined per area individual slides each ImageJ Fiji. mean total calculated week 0, 2 16, well duodenum 6 all markers. Finally, correlations between groups Pearson correlation (r). Results: All nine included female had limited cutaneous SSc. Groups receiving comparable duration found relative change SIR 0 differed group (Figure 1A, left panel). Similar changes observed anti-gp38, anti-CD38 anti-CD64 (left panel Figures 1B-D). Strong markers (r=0.98), anti-gp38 (r=0.94), anti-CD34 (r=0.85) (r=0.93) 1, A-D). group, there no (r=0.22) (r=0.21), however, strong (r=0.86) (r=0.92) 1A-D, right Conclusion: This data indicates different mucosa SSc affection. Interestingly, mucosal improved group. References: [1]Fretheim H, Chung BK, Didriksen Bækkevold ES, Midtvedt Ø, Brunborg C, et al. Fecal systemic sclerosis: A double-blind, placebo-controlled randomized trial. PLoS One. 2020;15(5):e0232739. Figure 1. Relative panel) ratios time point 16 weeks (right Acknowledgements: will like thank Maria Comazzi she have done IHC stainings Disclosure Interests: Henriette Speakers bureau: Travel bursary - GSK speaker Actelion, Noemi Strahm: None declared, Øyvind Molberg: Håvard Fretheim Received travel bursaries remuneration Bayer., Torhild Garen: Midtvedt: Oliver Distler Kymera Therapeutics, Mitsubishi Tanabe Pharma, Abbvie, Acceleron, Alexion, Amgen, AnaMar, Arxx Baecon Discovery, Blade Corbus Pharmaceuticals, Drug Development International Ltd, CSL Behring, Galapagos NV, Glenmark GSK, Horizon (Curzion) Inventiva, iQvia, Lilly, Novartis, Pfizer, Topadur UCB, Grant/research support from: Boehringer Ingelheim, Beyer, Gabriela Kania: Anna-Maria Hoffmann-Vold Roche, Bayer, Merck Sharp & Dohme, ARXX Medscape, Ingelheim