- Crohn’s disease is a condition that causes painful swelling in a person’s digestive tract.
- Scientists have been searching for more effective treatments as well as the underlying causes of the disease.
- Researchers now say it appears a common norovirus may be linked to a higher risk of developing Crohn’s disease.
- They hope their research can lead to better understanding of the condition as well as new treatments.
The origins of Crohn’s disease, a type of inflammatory bowel disease (IBD) that can cause painful swelling of the tissues in the digestive tract, have confounded scientists for years.
As many as 780,000 people in the United States have the condition, according to the Crohn’s & Colitis Foundation of America.
When a person has Chron’s disease, immune defenses in the body that are supposed to attack invading microbes mistakenly target the body’s own digestive tract instead.
Treatment modalities currently available can bring some relief, but they can also have a negative impact on the immune system and bring on multiple side effects.
The precise cause of Crohn’s disease remains unknown. And there is no known cure.
However, new research on mice as well as human tissue may have finally answered at least some of the nagging questions about how Crohn’s disease is triggered and how scientists might be able to treat it.
In the new study, Crohn’s disease is being linked to the common norovirus, a group of viruses that can cause gastroenteritis, an inflammation of the stomach and intestines.
What the study showed
The research, which was published in the journal Nature, revealed for the first time that in healthy people, T cells, which are part of the immune system, secrete a protein called apoptosis inhibitor 5 (API5), which signals the immune system to halt the attack on gut lining cells.
The AP15 protein produces an extra layer of protection against immune damage, so even people with the mutation can have a healthy gut, scientists say.
However, the researchers also found that a common norovirus infection blocks T cell secretion of API5 in mice bred to have a rodent form of Crohn’s disease, killing gut lining cells in the process.
Researchers at NYU Grossman School of Medicine said that API5 protects most people with the mutation against the disease until a second trigger, such as norovirus infection, pushes the disease across a threshold.
Ken Cadwell, Ph.D., a study co-senior author as well as a microbiologist and a professor of microbiology at NYU Langone, said that in experiments centered on mice genetically modified to have the mutation linked to Crohn’s disease in humans, the mice that received an injection of API5 survived while half of the untreated group died.
This, the study authors wrote, confirmed the hypothesis that the protein protects gut cells.
In human tissue, the investigators found that those with Crohn’s disease had between 5-fold and 10-fold fewer API5-producing T cells in the gut tissue than those without the condition.
What one expert thinks
Dr. David Rubin, a professor of medicine at the University of Chicago whose clinical expertise includes inflammatory bowel diseases, has discussed the study with two colleagues – an immunologist and a microbiologist who specializes in gamma-delta T cells.
“We have long thought and certainly see in practice that infections may trigger the onset of inflammatory bowel disease,“ Rubin told Healthline. “There is a paper showing a similar relationship between a viral infection and subsequent celiac disease.”
How that occurs has not been worked out, Rubin explained.
“So the hypothesis that there is an underlying genetic susceptibility in the protective factors related to our gut has been discussed and is of great interest,” he noted.
However, Rubin added, “I would be cautious in describing a mouse study has [in] answering questions about Crohn’s disease in humans, even with their organoid work that is part of this nice paper.”
Paneth cells have been of great interest in the pathogenesis as cause or effect of Crohn’s disease, he said.
“But the prevalence of this protective protein deficiency, at the tissue level, or even the mutations that are associated with impaired apoptosis have not been fully described in Crohn’s disease,” Rubiin said.
He added that gamma-delta T cells have important roles in our immune system but not the same role in the blood as in the gut tissue.
“The connection between those areas and observations of these cells certainly require additional work,” he said. “So I certainly congratulate the authors on this work – now let’s look across the many types of Crohn’s disease to see whether we can identify this further in humans.”
Could this lead to a new treatment?
Cadwell told Healthline that when the norovirus infects people with a weakened ability to produce API5, it tips the balance toward an autoimmune disease.
Potentially, the API5 protein or something similar could lead to a new treatment for Crohn’s that won’t break down the immune system, as many current treatments do, he said.
Cadwell cautioned that while the study authors derived API5 protein from human tissue rather than rodents, it is still not known whether the injection treatment can be safely administered in humans.
“There is a lot of work to do before we test this in humans,” Caldwell said.
“We are a couple of years away before this can go full speed ahead in clinical trials,” he added.
Current treatments are limited
Cadwell acknowledged that while Chron’s disease is not curable, there are some medications that work well for some people.
“One example is Remicade, which is also used to treat rheumatoid arthritis,” he said.
“But these treatments don’t always work, or they stop working, and the other issue is that these treatments compromise the immune system,” he added.
There are other treatments, ranging from antidiarrheal medicines and anti-inflammatory drugs to antibiotics to biological therapies to diets and supplements.
Dr. Yu Matsuzawa, a gastroenterologist and the lead author of the study, said in a press statement that he shares Cadwell’s enthusiasm about their findings.
“Our findings offer new insight into the key role that apoptosis inhibitor 5 plays in Crohn’s disease,” he said. “This molecule may provide a new target for treating this chronic autoimmune illness, which has proven difficult to manage over the long term.”
How Crohn's Disease Risk May Be Linked to Common Norovirus
Source: Pinoy Lang Sakalam
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