The role of a traitorous antibody in triggering inflammatory bowel disease has been described in detail in a new study published this month in the New England Journal of Medicine.
For the first time, researchers have linked a gene thought to be responsible for ulcerative colitis with a mechanism of attack, opening the way to new diagnostic tools and opportunities for treatment.
In the 1990s, scientists from the University of Oxford in the UK discovered a potential connection between the immune gene HLA-DRB1*01:03 and inflammatory bowel disease (IBD).
Now, in a study led by researchers from the same university, scientists have shown how the presence of HLA-DRB1*01:03 may give rise to the illness’s symptoms via a turncoat antibody that disrupts immune-suppressing communication between cells.
IBD is an umbrella term for Crohn’s disease and ulcerative colitis, conditions that severely affect millions around the world. As the name implies, these chronic forms of illness are the result of severe inflammation in the intestinal tract, potentially resulting in pain, diarrhea, bleeding, malnutrition, and weight loss, often to the point of requiring hospitalization.
Though environmental conditions are thought to play a role, IBD has strong genetic links; between 5% and 20% of individuals with the disease having a parent, child, or sibling who also suffers from the condition.
There are hundreds of genetic variations linked with the IBD, with some far more prevalent than others. Having a mutation in the gene responsible for producing the potent anti-inflammatory chemical interleukin-10, for example, is one of the more common risk factors for the disease, accounting for up to 85% of infantile IBD cases.
Interleukin-10 acts as a kind of cellular diplomat, mediating responses between cells to suppress reactions to pathogens and limit collateral damage to our own tissues. Without it, exposure to antigens such as those in food can result in a runaway storm of immune responses.
A few years ago, researchers discovered neutralizing autoantibodies against interleukin-10 in two children with IBD, raising the question of where these self-targeting antibodies may have come from, and whether they may “mimic” the loss of function in other immune-suppressing genes.
An analysis of around 5,000 patient samples in an Oxford and a UK IBD database suggests around 3.5% of people with the condition have these anti-interleukin-10 antibodies in their system, blocking its immune-suppressing response.
What’s more, there is a strong association between the presence of these antibodies and the gene HLA-DRB1*01:03.
Exactly how this gene variant raises the risk of producing antibodies against interleukin-10 could be explored in future research.
For now, knowing that the body can mount an attack against immune diplomacy and trigger severe inflammation in the bowel has implications for testing and treating conditions such as ulcerative colitis.
This research was published in the New England Journal of Medicine.
Source: University of Oxford via MedicalXpress
Fact-checked by Bronwyn Thompson
