A team led by LMU physician Daniel Kotlarz has identified a previously unknown genetic cause of Crohn’s disease.
Chronic inflammatory bowel disease is on the rise worldwide. Despite significant advances in diagnosis and treatment, the underlying causes of these diseases are often still poorly understood. An international research team from the VEO-IBD Consortium (a global research network supported by the Leona M. Helmsley and Harry B. Helmsley Charitable Trust), which includes LMU University Hospital and Toronto’s Hospital for Sick Children (SickKids), has identified a previously unknown genetic cause of chronic inflammatory bowel disease. The results were published in a magazine Gastroenterology.
The study involved researchers from Canada, Germany, the United States, China, Japan, France, Spain, and Saudi Arabia. “This study highlights the importance of international collaboration in understanding rare diseases and developing new treatments for chronic inflammatory bowel disease,” says Daniel Kotlarz, Heisenberg Professor of Pediatric Inflammatory Bowel Disease Precision Medicine at LMU University Hospital and one of the study’s corresponding authors.
Researchers have shown that pathogenic mutations exist in the gene. BIRC3 It can cause severe Crohn’s disease. During the study, they identified 14 patients from 10 different families who carried the pathogenic variant. BIRC3. Researchers have successfully elucidated the underlying disease mechanisms using state-of-the-art genetic, transcriptomic, and proteomic analyzes and experimental model systems.
According to research, BIRC3 This function leads to dysregulation of the RIPK1 signaling pathway in the intestinal epithelium. “Our results show for the first time how energy is lost. BIRC3 “The protective function of the patient’s intestinal mucosa is impaired and chronic inflammation is promoted,” said Xiang Shen, co-lead author of the study and a scientist at LMU University Hospital Von Hauner Children’s Hospital.
The significance of this discovery extends beyond rare genetic diseases. Researchers have found signs that the same signaling pathway may also play an important role in the more common form of Crohn’s disease. “This study impressively demonstrates the added value that international research networks can bring to the understanding of rare diseases.
“It was only through close collaboration between clinicians and researchers around the world that we were able to identify enough affected individuals to uncover new disease mechanisms and potential therapeutic targets,” explains Dr. Aleixo Muise, Senior Scientist at SickKids and Co-Director of the IBD Center, one of the leaders in the international research.
For the researchers, this study is an important step on the path to precision medicine for chronic inflammatory bowel disease.
A rare monogenic disease allows unique insight into the biological causes of chronic inflammatory bowel disease. discovery of BIRC3 Deficiency diseases not only result in new diagnoses for affected families, but also open up the possibility of new approaches to targeted therapy, which may also benefit larger patient groups in the future. ”
Daniel Kotlarz, Heisenberg Professor of Precision Medicine in Pediatric IBD, LMU University Hospital
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Ludwig Maximilian University of Munich (LMU)
Reference magazines:
Lee, Q. others. (2026). BIRC3 (encoding cellular inhibitor of apoptosis protein 2) variants cause dysregulation of receptor-interacting protein kinase 1 signaling, cause increased epithelial cell death, and are associated with monogenic Crohn’s disease. Gastroenterology. DOI: 10.1053/j.gastro.2026.05.022. https://www.gastrojournal.org/article/S0016-5085(26)06946-5/fulltext
