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New Light On the Genetic Basis of Inflammatory Diseases

Discussion in 'Other Health News and Research' started by Waverunner, Nov 2, 2012.

  1. Waverunner

    Waverunner Senior Member

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    This is just my personal opinion but for me it seems, that most diseases are puzzles. Many are highly complex (e.g. chronic diseases) and consist of many pieces. The pieces are made up of scientific findings. These findings take their time but lately it seems, that the pieces are getting bigger and fit very well to other pieces. This could be an unwarranted burst of optimism on my side but see for yourselves. Crohn's disease and Ulcerative Colitis have more in common, than previously thought. It seems that one key component of intestinal health is the ability of the immune system to distinguish between friendly and pathogenic bacteria. As soon as this mechanism gets disrupted, we see the big problem, that the immune system starts fighting friendly bacteria and thereby damages the gut as well as uses up needed resources. We don't know the cause for this but the consequences are unwanted, especially in the long run. They include inflammatory and autoimmune diseases but also weaken and impair proper functioning of the human body. How gut integrity plays into this, cannot be said for sure, but it probably takes its toll as well.

    http://www.sciencedaily.com/releases/2012/11/121101153601.htm

    ScienceDaily (Nov. 1, 2012) — In one of the largest studies of its kind ever conducted, an international team of scientists has thrown new light on the genetic basis of the inflammatory bowel diseases (IBD). Crohn's disease and ulcerative colitis, the two most common forms of IBD, are chronic inflammatory digestive disorders.

    Dr. John Rioux, researcher at the Montreal Heart Institute and Associate Professor of Medicine at the Université de Montréal, is one of the researchers who have identified 71 genetic regions newly associated with inflammatory bowel disease (IBD), increasing the total number discovered to date to 163, in one of the largest studies of its kind. Also, the study points out that these regions showed a striking overlap with those implicated in autoimmune diseases and in immune deficiencies. Even more surprising was the observation of a significant overlap with genetic regions controlling our response to microbial infections such as in the case of tuberculosis.
    The research was published Nov. 1 in the journal Nature.
    Moreover, these findings suggest that IBD results from overactive immune defence systems that evolved to fight off serious bacterial infections. In IBD, the body's immune system produces an ongoing inflammatory reaction in the intestinal tract that injures the intestinal wall, leading to diarrhea and abdominal pain. IBD patients typically require lifelong treatment with drug therapy, and often need surgery to repair tissue damage caused by the disease.
    Common research
    Up until this point, researchers have been studying Crohn's disease and ulcerative colitis separately. This study was based on the fact that there seems to be a vast amount of genetic overlap between the two disorders.
    In the first step of the study, the researchers conducted a "meta-analysis" of 15 previous genomic studies of either Crohn's disease (CD) or ulcerative colitis (UC), the two most common forms of IBD, creating a large dataset that combined genetic information from some 34,000 individuals who took part in those studies. The results then formed part of a second meta-analysis that included data from new genome-wide scans of more than 41,000 DNA samples from CD/UC patients and healthy comparison subjects collected at 11 centers around the world by the International IBD Genetics Consortium.
    "We have greatly expanded the map of genetic regions that are associated with IBD," agreed Dr. John Rioux, co-lead author of this study and chair of the Consortium, with Jeffrey Barrett of the Wellcome Trust Sanger Institute in Cambridge, England, lead author of the study. "Each of these regions only increases a person's chance of developing IBD by a fraction of a per cent and even taken together they cannot tell us who will or will not develop the disease. But they each tell a small story about the biology of this disorder, and by combining them we find biological pathways that, if disrupted, can lead to IBD."
    Immune system: a major factor
    Dr. Rioux and the international team of researchers also studied the activity of genes in their IBD regions in hundreds of different types of cells involved in the immune system. They found that certain cells tended to produce more of these IBD genes, including many that are involved in the body's first line defence against invasion. This illustrates that an immune response seems to be a major factor in IBD: when a bacterium is detected, these cells are not just activated, but become overactive.
    "We see a genetic balancing act between defending against bacterial infection and attacking the body's own cells," said Dr. Barrett. "Many of the regions we found are involved in sending out signals and responses to defend against bad bacteria. If these responses are over-activated, we found it can contribute to the inflammation that leads to IBD."
    Nearly 100 scientists in 15 countries contributed to the new work, which "highlights the incredible power that working together in a large team can have," said Barrett. "This would not have been possible without the thousands of DNA samples from patients with these conditions assembled by the International IBD Genetics Consortium. Collectively, our findings have begun to uncover the biological mechanisms behind this disease."
    About inflammatory bowel diseases
    IBD results from inflammation in the digestive system and affects 2.5 million people worldwide. With over 230,000 cases, Canada has among the highest frequency of people with IBD in the world. Although it can affect any age group IBD is more likely to develop in teens and adults between 15 and 30 years of age. IBD is a lifelong debilitating condition. It can have a devastating impact on the physical and social lives of those affected.
     
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  2. Mark

    Mark Acting CEO

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    It's certainly exciting that there's so much interest in this, and apparently a lot of progress. However, there's a big problem to be overcome as well: we don't really know anything about why - or even whether - the immune system really is being 'overactive' as is often assumed. Perhaps there is a cause for the overactivity, and when you reduce the activity, you'll run the risk of allowing some stealth infection to go unchecked, or leave the body vulnerable to downstream effects of whatever the allergic response was trying to protect it from. This is a complex system we're interfering with, and relief of the immediate symptoms may well be considerably less than the whole picture. All that 'sickness behaviour' may conceivably be what's protecting some of us from cancer, or death by other means. I think those safety considerations might come more to the fore as treatments get closer to public roll-out. Don't want to be negative, but I think that note of caution is called for...
     
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  3. Enid

    Enid Senior Member

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    I've no doubt in the light of present pathological findings the immune system is knocked "sideways" but I'm seventy five (12 years ME) - so how after good health overcome completely - much more to it than genes.
     
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  4. Waverunner

    Waverunner Senior Member

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    Mark, I completely agree. Some people take all kinds of supplements and medication as long as it says "anti-inflammatory" on the label. The possibility, that the inflammatory reaction is actually protecting them, doesn't seem to come to their minds. It's a long and troublesome way, in order to find real solutions for chronic diseases like CFS. One of the most important parts will be the invention and usage of new diagnostic means (e.g. Nanosphere). We need high sensitivity and specificity of tests, as well as high efficiency and low cost. As soon as we can test for hundreds of viruses and bacteria, with one single, highly accurate but cheap test, we will be able to conduct much more studies, create much more useful data and hopefully come to a breakthrough. Finding out the causes for certain diseases will enable the search for the optimal treatment.
     
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  5. Enid

    Enid Senior Member

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    Yes I agree the old (long battle) with viruses and I think in cases such as ME overcome the immune system (many illnesses involved) - so immune research understanding and the blighters very welcome. I've aunts living to their 95s- 100s - blaming genes seems an opt out. and I really cannot recall any of them having anything "inflammatory" more than decline of age.
     
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  6. Mark

    Mark Acting CEO

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    Hmm...I have a little sympathy for the application of my argument to inflammation - the body doesn't cause inflammation for no reason, I think, it's an attempt to protect - but from what I was told (and my own experience) about back pain, inflammation can also be highly damaging system-wide. If you have chronic inflammation, for instance for persistent neck pain or back pain, that's actually doing damage in itself, both at the local site of the problem, and throughout the body. That's my understanding, anyway: the back pain clinic that was so helpful to me was really keen to emphasise that avoiding anti-inflammatories for these kind of reasons is a big mistake.

    My concern about treating auto-immunity by shutting off general components of immune reactions is twofold: firstly it might also switch off necessary and appropriate immune reactions, and secondly it might enable some long-term stealth pathogen that the 'auto-immunity' was responding to. In the latter case, this might be something that causes effects 10 or 20 years down the line...which means there's a difficult trade-off (or a gamble) to be made, and also means that this effect won't show up at all in trial results unless they are very large, long-term and looking in great detail. So it's very hard to be confident on the long-term safety of that kind of intervention.

    Having said that, in the case of someone of Enid's age, or somebody who is bedbound and has little quality of life anyway, it's much more likely to be a gamble worth taking.
     
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  7. Enid

    Enid Senior Member

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    No doubts about genetic predisposition/weakness in the immune system overcome by one pathogen or another - eventually. But that is my family - ME (brother and self) and cousin Fibrom. all previously very healthy - hunt what tips the balance will be the most revealing. And sure it has to do with those faulty B cells...age or not. That is the least important as so many children afflicted reveal. What switches (infections ?) the genes. Clearly age at onset is not an important factor.


    .
     
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