RNA-Seq after surgery to heal inflamed gut reveals a new target for disease

J-Pouch Surgical Procedure Can Lead to Inflammation Similar to Ulcerative Colitis

Led by researchers at NYU Grossman School of Medicine, the new investigation showed that some immune cells attacking the colon in ulcerative colitis are the same types attacking the J-pouch. Several varieties of immune cells were found swarming both organs in numbers as high as five times those seen in healthy tissue.

“Our findings suggest that since ulcerative colitis and pouchitis are biologically similar, they may be treated by the same drugs, even though the diseases originate in different parts of the gut,” says study co-lead author Jordan E. Axelrad, MD, MPH. Dr. Axelrad is an assistant professor in the Department of Medicine at NYU Langone Health.

He says starting with the most promising drugs can give medical providers a head start at combating pouchitis and avoiding complications from delayed treatment.

“With our newfound understanding of pouchitis, we can also begin to uncover why some people develop it in the first place and how to prevent it,” adds study co-lead author Joseph Devlin, MS, a doctoral candidate at NYU Langone.

For their investigation, published online December 21, 2020, in the journal Gastroenterology, the research team collected tissue samples from 15 men and women who had J-pouch surgery, of whom 10 developed pouchitis. They compared the gene activity in pouch tissue from these patients with colon tissue samples from 11 patients with ulcerative colitis who did not have J-pouch surgery.

Investigators also analyzed the gene activity of 56,000 individual cells using an experimental method called RNA sequencing. They say it is the most detailed analysis of the pouchitis cellular immune response to date, and enabled them to track step-by-step genetic activity in a single cell in any given moment.

“Since using this RNA-sequencing technique has improved our understanding of treatment options for one kind of inflammatory bowel disease, we can likely use it to assess how effective treatments are for related issues like Crohn’s disease,” says study co-senior author Ken H. Cadwell, PhD.

Transcriptional Atlas of Ileal-Anal Pouch Immune Cells from Ulcerative Colitis Patients | bioRxiv

Dr. Cadwell, a member of the Skirball Institute of Biomolecular Medicine at NYU Langone, cautions that since the investigation focused only on immune cells, it remains unclear how other cells within the J-pouch, such as those that make up the organ’s lining, may behave during pouchitis.

He adds that the research team plans to evaluate the same patients before and after J-pouch surgery to see how the immune cell landscape changes over time as inflammation develops. Dr. Cadwell is also an associate professor in the Departments of Microbiology and Medicine at NYU Langone.

Source – NYU Langone Health

Devlin JC, Axelrad J, Hine AM, Chang S, Sarkar S, Lin JD, Ruggles KV, Hudesman D, Cadwell K, Loke P. (2021) Single Cell Transcriptional Survey of Ileal-Anal Pouch Immune Cells from Ulcerative Colitis Patients. Gastroenterology [Epub ahead of print]. [abstract]

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