April 11, 2024

Study Identifies New Predictor of Severe Pediatric Crohn’s Disease

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On Feb. 22, the Journal of Clinical Investigations published a study on the discovery of a new predictor of severe pediatric Crohn’s disease.

MicroRNAs are small molecules that help regulate gene expression in cells. Crohn’s is an increasingly prevalent disease characterized by chronic inflammation of the gut. It causes symptoms that can lead to malnutrition and fatigue and can be severe. 

“There’s a serious need to better understand how this disease develops and come up with better therapies,” said Prof. Praveen Sethupathy, biomedical sciences, the senior author of the study. 

MicroRNAs have known potential to serve as indicators of severity of disease and diagnostic markers in adults with Crohn’s disease, but their role in pediatric Crohn’s isn’t as well studied. 

To better understand the mechanisms of pediatric Crohn’s, Sethupathy and his team investigated the role of micro-RNAs in severe Crohn’s disease, collaborating with researchers at the University of North Carolina at Chapel Hill.

Looking at microRNAs in the gut samples of a large cohort of healthy children and in children diagnosed with Crohn’s disease, researchers found that 58 micro-RNAs differed between the two groups. One of them, miR-29, was found to be predictive of severe disease. 

“[There was a] correlation with miR-29 and a couple others with association with disease severity, [but] only miR-29 was shown to be specific to pediatric Crohn’s,” said Alexxandria Shumway grad, the first author on the study.

To follow up on their results, the researchers genetically engineered mice to overexpress miR-29. The goal was to see how this overexpression would affect inflammation in the gut. 

“We were broadly looking across a lot of different cell types in the intestinal lining,” Sethupathy said. “It was the Paneth cells that really stuck out as being dramatically changed in the context where we were elevating the microRNA.”

Elevated levels of miR-29 caused decreased amounts of Paneth cells, which are cells that have antimicrobial properties in the small intestine. Higher levels of miR-29 also caused lower expression of the tight junction protein Pmp22, which can result in compromised barrier integrity in the gut and more inflammation. 

Resolution of miR-29 as a key driver in inflammation in pediatric Crohn’s can have critical applications for diagnoses and may provide direction for further studies. 

Shumway cites her best friend’s diagnosis with Crohn’s in middle school as a key motivator for her participation in Crohn’s research. She hopes the use of miR-29 as a potential diagnostic tool may help improve the quality of care for other pediatric patients.

Kiran Kadakia ’26 was diagnosed with Crohn’s disease in middle school, and for him, getting diagnosed was a significant challenge. 

“The idea of Crohn’s disease was something my family wasn’t super conscious of. For a while I was just kind of dealing with the malnutrition and bouts of exhaustion without exactly knowing why it was [happening],” Kadakia said. “That initial discovery process was the most challenging part of my journey.”

Kadakia hopes that this research will improve public understanding about the disease and aid medical professionals in early diagnostic stages.

I think anything that boosts awareness of Crohn’s disease or boosts the doctors ability to be like, ‘Oh is this going to be something that’s very severe,’ [will be] very useful.”

High miRNA levels may suggest severe disease and can shorten trial medication periods or lead to earlier surgical intervention, according to Shumway. For patients with more severe Crohn’s, use of biomarkers like these may help doctors to characterize the severity of the disease and identify appropriate treatments sooner. 

However, there are some nuances to the study. 

“In late stages in the disease, having lots of miR-29 might be helpful, but in early stages of the disease having lots of miR-29 might be problematic,” Sethupathy said. 

Further research investigating the role of miR-29 is needed to determine the next steps in developing potential therapies for pediatric patients.

Emma Arboleda can be reached at [email protected].