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- Jul 11, 2014
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I'm summarizing some papers I recently read. It talks about new observations of a possible cause that was first hypothesized many decades ago.
Immunologist at Washington University St. Louis [1] are looking at possibility that something going awry in the intestinal lymphatic system may underlie Crohn's disease. Using advanced 3D microscopy to view long segments of intestinal tissue, they observed that the lymphatic system of CD patients was altered and key vessels were often constricted. NIH has provided an award for the researchers to pursue this promising lead.
The Kruningen paper [2], walks back an interesting history of earlier research and pathology findings in Crohn's Disease, where they were able to look at treatment naive tissue samples that were not altered or distorted from use of steroids, immunomodulators and biologics. What they observed was segmental distribution of changes below lymphoid follicles of Peyer's patches, in the basal portions of the lamina propria, and in the submucosal layers of the intestine. These lesions are lymphocitic thrombi and large collections of lymphocytes often containing granulomas, all characteristics of chronic lymphangitis.
The Kruningen paper goes on to describe how another researcher, TV Kalima, carried on an experiment in both rats and pigs, where they manually obstructed short segments of the lymphatics of the small intestines, and the animals developed segmented intestinal disease characterized by the same sort of changes observed in Crohn's Disease. Namely, aggregation of lymphocytes, thickening of the intestinal walls, and development of fistulas. They point out that no animal model has been able to achieve such resemblance to Crohn's Disease, and many of the current animal experimental models where they use agents such as dextran sodium sulfate to simulate damage only effects the mucosal layer but doesn't exhibit the transmural regional enteritis that you see in Crohn's.
This research is suggesting exploration of whether lymphocytic, granulomatous lymphangitis may be the triggering cause of Crohn's Disease, and if so, what agents (bacteria, viruses, particles) target the lymphatic endothelium to trigger the disease.
[1] Creative Minds: New Piece in the Crohn's Disease Puzzle?
https://directorsblog.nih.gov/2016/06/09/creative-minds-new-piece-in-the-crohns-disease-puzzle/
[2] The forgotten role of lymphangitis in Crohn's disease
H J Van Kruiningen, Jean-Fre´de´ric Colombel
Immunologist at Washington University St. Louis [1] are looking at possibility that something going awry in the intestinal lymphatic system may underlie Crohn's disease. Using advanced 3D microscopy to view long segments of intestinal tissue, they observed that the lymphatic system of CD patients was altered and key vessels were often constricted. NIH has provided an award for the researchers to pursue this promising lead.
The Kruningen paper [2], walks back an interesting history of earlier research and pathology findings in Crohn's Disease, where they were able to look at treatment naive tissue samples that were not altered or distorted from use of steroids, immunomodulators and biologics. What they observed was segmental distribution of changes below lymphoid follicles of Peyer's patches, in the basal portions of the lamina propria, and in the submucosal layers of the intestine. These lesions are lymphocitic thrombi and large collections of lymphocytes often containing granulomas, all characteristics of chronic lymphangitis.
The Kruningen paper goes on to describe how another researcher, TV Kalima, carried on an experiment in both rats and pigs, where they manually obstructed short segments of the lymphatics of the small intestines, and the animals developed segmented intestinal disease characterized by the same sort of changes observed in Crohn's Disease. Namely, aggregation of lymphocytes, thickening of the intestinal walls, and development of fistulas. They point out that no animal model has been able to achieve such resemblance to Crohn's Disease, and many of the current animal experimental models where they use agents such as dextran sodium sulfate to simulate damage only effects the mucosal layer but doesn't exhibit the transmural regional enteritis that you see in Crohn's.
This research is suggesting exploration of whether lymphocytic, granulomatous lymphangitis may be the triggering cause of Crohn's Disease, and if so, what agents (bacteria, viruses, particles) target the lymphatic endothelium to trigger the disease.
[1] Creative Minds: New Piece in the Crohn's Disease Puzzle?
https://directorsblog.nih.gov/2016/06/09/creative-minds-new-piece-in-the-crohns-disease-puzzle/
[2] The forgotten role of lymphangitis in Crohn's disease
H J Van Kruiningen, Jean-Fre´de´ric Colombel
