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Possible biomarker for IBS-D

Kyla

ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ
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721
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Canada
http://www.nature.com/nature/journal/v533/n7603_supp/full/533S110a.html?WT.mc_id=TWT_OUTLOOK_IBS

Posting this not only because many have co-morbid IBS, but because this is an interesting discussion of the chicken/egg problem with biomarkers, definitions and subgroups.
I think a very relevant discussion as regards ME & CFS



Excerpt:
Diagnostics: Filling in the missing pieces
Nature 533, S110–S111 (19 May 2016) doi:10.1038/533S110a
Published online 18 May 2016

For years, researchers have tried to find biomarkers that could aid the diagnosis of irritable bowel syndrome, and point to its underlying causes. But will one test ever be enough?

Sarah J. Coleman

It was a hunch almost two decades ago that launched Mark Pimentel's interest in irritable bowel syndrome (IBS). Back then, despite the prevalence of the condition, people with IBS were often told that their symptoms were all in their heads. But Pimentel, then a gastroenterology fellow at Cedars-Sinai, a medical center in Los Angeles, California, focused elsewhere in their bodies, on the rumblings in the abdomen: bloating, distension and flatulence — in short, gas.

Pimentel wondered whether bacteria fermenting food in the gut were producing an excess of gas. In 2000, along with his mentor, Henry Lin, Pimentel reported that almost 80% of people with IBS harboured an overgrowth of bacteria in their small intestines1. For about half of these patients, eradicating the extra bacteria improved symptoms. Around that time, other groups were also making bacterial connections — linking food poisoning to IBS. In the same vein, when Pimentel and his colleagues infected rats with the bacterium Campylobacter jejuni, a common cause of travellers' diarrhoea, they found that the animals developed not only IBS-like symptoms, but also similar bacterial overgrowth2. That's where things began to get interesting, says Pimentel, who now directs the gastrointestinal-motility programme at Cedars-Sinai. “From that point on, we said, 'OK, something in these bugs is causing IBS'.”

The culprit, Pimentel says, is cytolethal distending toxin B (CdtB), a key part of a toxin produced by pathogens that cause gastroenteritis. Last year, Pimentel reported that in a model of IBS, rats infected with C. jejuni formed antibodies to CdtB, which in turn triggered an autoimmune response against cells of the gut wall3. Furthermore, he found that blood-plasma levels of CdtB antibodies could help to distinguish people with diarrhoea-predominant IBS (IBS-D) from those with inflammatory bowel disease or coeliac disease and from healthy controls4. With these results in hand, Pimentel and diagnostics company Commonwealth Laboratories of Salem, Massachusetts, developed a blood test called IBSchek. “We've never had a biomarker that says, if you're positive, you have IBS,” Pimentel says. “This is that test.”

People with IBS need a diagnostic test. Patients get the label only when diseases that have similar symptoms, such as Crohn's disease, coeliac disease or colorectal cancer, are excluded. The current system can leave people in diagnostic limbo — the average time to diagnosis is 6.6 years5, during which they shuttle between doctors and undergo multiple tests, and still end up not quite being able to say that they have a disease (see page S112). Multiple attempts have been made to identify markers that could provide a positive diagnosis, but with limited success. In 2009, a team that included Anthony Lembo, a gastroenterologist at Beth Israel Deaconess Medical Center in Boston, Massachusetts, who went on to be a co-author of the 2015 CdtB-antibody clinical study, launched a 10-biomarker blood test for IBS with pharmaceutical company Prometheus Laboratories. But the test is no longer being sold. The main problem, says Lembo, was that the markers in the panel weren't related to what caused IBS...

you can read the rest here:
http://www.nature.com/nature/journal/v533/n7603_supp/full/533S110a.html?WT.mc_id=TWT_OUTLOOK_IBS
 
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2,087
Back then, despite the prevalence of the condition, people with IBS were often told that their symptoms were all in their heads.

Isn't it still the case ?
A psychological diagnosis in IBS is as equally daft as ME.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
@Jonathan Edwards, you might be interested regarding links between infection and auto-immunity.

This seems to be something of a throwaway remark from Dr Tack, and it seems he is not convinced in this case!

'Pimentel's hypothesis that an antibody generated by a bacterial toxin has autoimmune properties is sound, and well-supported by animal studies, Tack says. But he is not yet convinced that this antibody causes IBS, saying that there is no independent evidence that the participants in Pimentel's 2015 study really did have post-infectious IBS. '

The idea of cross reactivity is ingrained in the folklore. You can create cross reactivity in animals by giving vast doses of adjuvants, but you usually get a subacute monophasic post challenge illness, not like human autoimmunity. The only disease that looks reasonably like cross reactivity in humans is Guillain Barre and even that is monophasic as a rule. I am not terribly impressed by an antibody that binds to vinculin. Vinculin is one of those proteins that tends to pick up antibodies like static electricity picks up dust. I will wait and see!