Их Британи болон Данийн судлаачид 30 жилийн турш тодорхойгүй байсан гэдэсний үрэвсэлт өвчний (IBD) гарал үүслийг тайлбарлах чухал нээлт хийснээ The New England Journal of Medicine сэтгүүлд нийтэлжээ.
Судлаачид IBD-тэй 4,900 орчим болон эрүүл 1,000 орчим хүний цусны дээжийг шинжилж, HLA-DRB1*01:03 генийн хувилбар нь үрэвслийг хянадаг интерлейкин-10 (IL-10) уургийг саармагжуулдаг эсрэг бие үүсгэхэд нөлөөлдгийг тогтоожээ. IBD-тэй өвчтөнүүдийн 3.5 хувьд нь энэхүү саармагжуулагч эсрэг бие илэрсэн бол эрүүл хяналтын бүлэгт огт илрээгүй байна. Тодруулбал, Кроны өвчтэй хүмүүсийн 2.5 хувь, шархлаат колиттай хүмүүсийн 4.4 хувь нь уг эсрэг биеийг тээж байжээ.
Оксфордын их сургуулийн хүүхдийн гастроэнтерологич Holm Uhlig-ийн тэмдэглэснээр, энэхүү судалгаа нь IBD-ийн хүнд хэлбэрүүдтэй холбоотой байсан генетикийн хувилбар болон IL-10-ын аутоиммун хариу урвалын хоорондох холбоосыг нээж өгсөн юм. Энэхүү нээлт нь өвчний шалтгааныг тодорхойлж, цаашид өвчтөнүүдийг эрт үед нь оношлох, зорилтот эмчилгээ хийх боломжийг бүрдүүлж байна.
IBD-ийн одоогийн эмчилгээний аргууд нь зөвхөн шинж тэмдгийг намдаах эсвэл мэс заслын аргаар шийдвэрлэхэд чиглэдэг тул өвчнийг бүрэн эдгэрэх эмчилгээ одоогоор байхгүй. Гэсэн хэдий ч судлаачид энэхүү олдвор нь өвчний механизмыг илүү нарийвчлан ойлгож, эмчилгээний шинэ, үр дүнтэй арга замыг боловсруулахад чухал ач холбогдолтой гэж үзэж байна.
Дэлгэрэнгүйг эх сурвалжаас харах
↓Эх сурвалжийг нээх ↓
Inflammatory bowel disease (IBD) is a real pain in the gut.
Scientists have been working long and hard to identify the root causes of IBD, to improve treatments for what is actually a set of related, debilitating chronic conditions.
Now, new research has given us a significant breakthrough.
The discovery, courtesy of a team of researchers in the UK and Denmark, solves a 30-year mystery: Why is one particular gene variant, HLA-DRB1*01:03, associated with IBD?
Studies showed that this version of the HLA-DRB1 gene was more common in IBD patients, particularly those with severe disease. But it wasn’t clear what effect this genetic quirk had – how it possibly contributed to IBD.
Now we have an answer: Having the HLA-DRB1*01:03 variant means a person with IBD is more likely to produce antibodies that mistakenly attack interleukin 10 (IL-10), an important chemical messenger that helps keep inflammation in check.
Like the HLA-DRB1*01:03 variant, mutations in the genes that code for IL-10 have been linked with IBD before, but this latest study joins some of the dots.
“We’ve suspected an important role of interleukin 10 in patients with inflammatory bowel disease for decades,” says pediatric gastroenterologist Holm Uhlig, from the University of Oxford.
“The study now provides clear evidence and contributes the missing link between a well-known genetic variant that had been linked to severe inflammatory bowel disease in the past and the very recently discovered autoimmunity to interleukin 10.”
To solve the puzzle, the researchers began by testing blood samples from roughly 4,900 people with IBD and some 1,000 people without, looking for signs of antibodies that neutralize IL-10.
These antibodies were present in around 3.5 percent of IBD patients, but in none of the healthy controls.
Teasing apart the differences further, around 2.5 percent of those with Crohn’s disease and 4.4 percent of those with ulcerative colitis – the two main types of IBD – had neutralizing antibodies in their blood.
It suggests that IBD could be driven, in a substantial number of people, by antibodies that release the ‘brake’ on inflammation that IL-10 usually applies.
Next, the researchers looked at the genetics of people with IL-10 antibodies versus those without. That led them to HLA-DRB1*01:03, which was very strongly associated with the IL-10 antibody subgroup.
“This is the most exciting discovery in a lifetime specializing in IBD,” says clinical gastroenterologist Simon Travis, from the University of Oxford.
“It means that we can now identify a group where we know what is causing the disease and that creates a real opportunity to change how we manage this disease.”
IBD affects millions of people worldwide, and the number of cases keeps on rising.
Even if these new findings apply only to a small percentage of IBD patients, that would still work out to be a significant number of people globally.
Notably, the chain of evidence that the researchers assembled here all started with an analysis of relatively rare and severe cases of IBD, that were at first linked to genetic defects in IL-10 or its receptor, and later, the presence of neutralizing antibodies.
“This discovery shows how the study of rare, inherited disorders can shed new light on common conditions,” says immunologist Sophie Hambleton, from Newcastle University in the UK.
Like other complex conditions, IBD manifests in myriad ways. This study adds to what we already know about IBD, and there may well be different causes for different types.
Previous studies have highlighted the role of overactive, rogue immune cells causing inflammation in ulcerative colitis.
Other work has revealed certain gene variants in Crohn’s disease rob immune cells of their natural defenses, similar to what was found here.
Appreciating those differences could help guide the development of specific, new treatments.
Related: Newly Identified Molecule Can Heal Gut Damage And Suppress Cancer
Right now, treatments for IBD include drugs to manage the symptoms of these conditions, and in some serious cases, surgery. None of these approaches count as effective cures, though, meaning new treatments are badly needed.
“By identifying patients early and giving them targeted treatment, we could reduce reliance on expensive ongoing therapy and prevent complications,” says clinical immunologist Rainer Doffinger, from Cambridge University Hospital.
The research has been published in The New England Journal of Medicine.
