MedUni Vienna: Progress made in understanding Crohn's disease

Crohn's disease is a chronic inflammatory bowel disease that is sometimes insufficiently controlled by immunosuppressive therapies with a subsequent need for surgical removal of affected bowel segments. By analysing draining mesenteric lymph nodes of affected small intestinal segments of patients who had required surgery, a research team led by Lukas Unger from MedUni Vienna identified immune responses that improve our understanding of the disease. The results of the study have just been published in the journal "Cellular and Molecular Gastroenterology and Hepatology".

Recent studies had investigated immune responses in mesenteric lymph nodes in models of ulcerative colitis, another chronic inflammatory bowel disease that exclusively affects the large intestine. The insufficient data available to date on Crohn's disease, which often manifests itself in the last section of the small intestine but spares the large intestine, forms the background to the research carried out by Lukas Unger and his team from MedUni Vienna's Department of General Surgery. The starting point was the question of why and against what Crohn's disease patients develop antibodies against many antigens that do not occur in healthy people.

B-cell reactions investigated

The scientists discovered the answer by comparing lymph nodes from inflamed and non-inflamed segments of the patient's small intestine: This showed that a certain type of immune cell (B cells) mature in sections affected by Crohn's disease in a quantity and in a way that is not detectable in the patients' healthy intestinal segments. "Even just a few centimetres away from the affected areas, we were unable to detect this altered immune response," says study leader Lukas Unger, emphasising the special aspect of the research work, the first scientific examination of B-cell receptors in lymph nodes in Crohn's disease. Previous studies had been limited to blood samples, which do not adequately represent the immune response in the tissue.

Investigating precise mechanisms in future research

The results form the basis for further research, particularly into the exact mechanisms and the question of how these altered B-cell responses in Crohn's disease patients influence the clinical course after surgery. In addition, new therapeutic strategies could be developed based on the findings. The current study was conducted in collaboration between the MedUni Vienna team and colleagues from the University of Cambridge (UK), where Lukas Unger completed his postdoctoral stay from 2019-21.

Publication: Cellular and Molecular Gastroenterology and Hepatology

Altered B-Cell Expansion and Maturation in Draining Mesenteric Lymph Nodes of Inflamed Gut in Crohn’s Disease;
Sonja Kappel-Latif, Prasanti Kotagiri, Lukas Schlager, Gabor Schuld, Natalie Walterskirchen, Vanessa Schimek, Gavin Sewell, Carina Binder, Johanna Jobst, Supriya Murthy, Barbara Messner, Stefanie Dabsch, Arthur Kaser, Paul A. Lyons, Michael Bergmann, Anton Stift, Rudolf Oehler and Lukas W. Unger;

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