Major cause of inflammatory bowel disease discovered

Sub : Science and tech

Sec: Health

Tags: inflammatory bowel disease, Autoimmune Disorders

Context:

Researchers at the Francis Crick Institute, working with UCL and Imperial College London, have discovered a new biological pathway that is a principal driver of inflammatory bowel disease (IBD) and related conditions, and which can be targeted using existing drugs.

Key Highlights:

About 5% of the world’s population, and one in ten people in the UK1, are currently affected by an autoimmune disease, such as IBD, the umbrella term for Crohn’s disease and ulcerative colitis.
These diseases are also becoming more common, with over half a million people living with IBD in the UK as of 2022, nearly double the 300,000 previously estimated2.
They found that this gene desert contains an ‘enhancer’, a section of DNA that is like a volume dial for nearby genes, able to crank up the amount of proteins they make.
The team discovered that this particular enhancer was only active in macrophages, a type of immune cell known to be important in IBD, and boosted a gene called ETS2, with higher levels correlating with a higher risk of disease.
The scientists showed that ETS2 was essential for almost all inflammatory functions in macrophages, including several that directly contribute to tissue damage in IBD.

ETS2 as a treatment target:

They found that MEK inhibitors, drugs already prescribed for other non-inflammatory conditions, were predicted to switch off the inflammatory effects of ETS2.
As MEK inhibitors can have side effects in other organs, the researchers are now working with LifeArc to find ways to deliver MEK inhibitors directly to macrophages.

What is Crohn’s disease?

Crohn’s disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract.
Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss.
Complications outside of the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and fatigue.
The skin rashes may be due to infections as well as pyoderma gangrenosum or erythema nodosum.
Bowel obstruction may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer and small bowel cancer.

What are Autoimmune Disorders?

An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms.
It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions.
Autoimmune diseases are a separate class from autoinflammatory diseases.
Both are characterized by an immune system malfunction which may cause similar symptoms, such as rash, swelling, or fatigue, but the cardinal cause or mechanism of the diseases are different.
A key difference is a malfunction of the innate immune system in autoinflammatory diseases, whereas in autoimmune diseases there is a malfunction of the adaptive immune system.
Some of the most common diseases that are generally categorized as autoimmune include celiac disease, type 1 diabetes, Graves’ disease, inflammatory bowel diseases (such as Crohn’s disease and ulcerative colitis), multiple sclerosis, alopecia areata,Addison’s disease, pernicious anemia, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.
Diagnosing autoimmune diseases can be challenging due to their diverse presentations and the transient nature of many symptoms.