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Autoantibodies — rogue immune proteins — may be to blame for some cases of IBD.(Image credit: Stocktrek Images via Getty Images)
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The origins of inflammatory bowel disease (IBD) are not well understood, but scientists have now identified an overactive immune response that might be responsible for the condition in certain individuals.
IBD, characterized by persistent inflammation throughout the digestive tract, impacts millions globally. Its primary forms include Crohn’s disease, which can affect any part of the gastrointestinal tract, and ulcerative colitis, which is limited to the colon and rectum.
Although IBD patients may exhibit comparable inflammation, the root cause can differ. Recognizing these distinctions could potentially pave the way for novel, targeted therapeutic approaches, the researchers suggested in the recent study.
“Early identification of these patients could eventually enable clinicians to expedite treatments that address the specific disease mechanism, rather than relying on a sequential, trial-and-error approach with medications,” Dr. Brad Pasternak, medical director of the IBD Clinic at Phoenix Children’s Hospital, who was not involved in the research, informed Live Science via email.
A potential subtype of IBD
The genetic landscape of IBD is intricate, with prior investigations linking the condition to 300 genomic “hotspots.” The most significant known genetic predisposition for ulcerative colitis is a gene variant known as HLA-DRB1*01:03, yet its precise contribution to IBD has remained elusive.
The latest study, released on June 10 in The New England Journal of Medicine, helps to connect these findings.
A crucial piece of evidence emerged from earlier work by the same research group, which examined the blood of two children diagnosed with IBD. These children possessed autoantibodies — immune system proteins that attack the body’s own tissues instead of pathogens — which were inhibiting a vital anti-inflammatory protein known as interleukin-10 (IL-10).
IL-10 typically functions by suppressing the release of pro-inflammatory proteins. Therefore, individuals whose bodies obstruct IL-10 effectively release a mechanism that should be restraining inflammation, Pasternak explained.
The researchers hypothesized that these autoantibodies might be a contributing factor to IBD. In their most recent investigation, they aimed to determine if a larger cohort of IBD patients exhibited the same autoantibodies.
The study incorporated data from over 4,900 individuals with IBD and more than 1,000 without the condition. Employing two distinct laboratory assays, the researchers analyzed blood samples from both groups, detecting the autoantibody in 173 of the IBD patients, approximately 3.5%. The autoantibody was found to be virtually absent in the blood of the control group.
Subsequently, in laboratory experiments, the team exposed immune cells to blood from IBD patients carrying the autoantibody. This resulted in a reduction of IL-10 levels and induced a pro-inflammatory response.
Dr. Holm Uhlig, a pediatric gastroenterologist at the University of Oxford and co-author of the study, indicated to Live Science that elucidating the drivers behind autoantibody formation will be a “focus of intense interest.” For the present, however, their findings suggest that patients with the HLA-DRB1*01:03 variant are considerably more prone to possessing autoantibodies that block IL-10 compared to those without the variant.
Historically, this variant has been associated with severe IBD requiring significant surgical intervention. “Currently, autoimmune responses are not at all part of the therapeutic repertoire, and that’s why we feel it’s a relevant study,” Uhlig stated.
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Uhlig also remarked that the identified subgroup of 3.5% of patients represents a “significant number,” considering the vast global prevalence of IBD.
Generally, many individuals with IBD are presently treated with medications that broadly suppress inflammatory pathways, Pasternak noted. However, treatment efficacy varies among patients. This research suggests a potential future pathway for customizing treatments based on the specific mechanism driving an individual patient’s disease, he added.
Beyond enabling personalized IBD treatments, Uhlig believes their discoveries may lead to improved diagnostic methods.
“Patients could undergo genetic testing already in the early stage of their disease diagnosis,” he proposed, “and then it would determine their susceptibility to develop autoantibodies.”
