@maurader
If it was “as simple as that” then both the disease and the targets would be well understood. More so if it were “as simple as that” then we would know exactly what host tissues the immune response is directed at. And even more so there would no longer be any debate on the topic itself. This is simply not the case at all.
In regards to environmental factors - I will just simply paraphrase a recent pathologists response - “Association is not causation”
If someone perhaps takes an immunology course or something of that nature or
opens an immunology text book you will rarely (most likely never) see Inflammatory Bowel Disease listed under the heading of autoimmune diseases. You may see a side note that says “suspected” but more likely now a days you will hear the professor speak of bacterial imbalance or dysbiosis as a possible suspected cause of Inflammatory Bowel Disease amongst other possible causes. Bacterial imbalance and the gut microbiota are quite the hot topic and field right now due to full genome sequencing.
You’ll often read an abstract where they start of by saying something like “Inflammatory Bowel Disease is an auto-immune condition characterized by….” This is actually a mis-use for the time being. It is simply a statement of the authors opinion. You will also read equally as many abstracts that start off with something like “Inflammatory Bowel Diseases are diseases of unknown etiology that are characterized by….” I feel, (personally), that this is perhaps the most correct way to begin as it is the truth at this point in time. This misuse of the statement “Inflammatory Bowel Disease in an auto-immune condition characterized by” get’s picked up by, and just confuses us as patients. We identify with the fact that we take immune suppressants and sometimes we get a bit better and sometimes we even land in remission and assume this means that we are suppressing the “auto-immune reaction” . Does this in any way mean we have an auto-immune condition for certain? No. What we are actually doing is simply “dampening” the inflammatory immune response with our medications. This means we, for some currently unknown reason have excessive inflammation and addressing or dampening this results in a reduction of symptoms. We all get the idea behind it - but it leads us to believe that IBD has in fact been 100% proven to be a true autoimmune condition and again this is not the case.
So a heck of a lot remains completely unknown at the moment. Still. After 100 years and 63,000 odd papers and studies.
Granted a ranging percentage of Ulcerative Colitis patients do in fact seem to have some auto-anibodies present - and I assume you are referring to p-ANCA and a few others like Anti Intestinal Globlet Cell Auto-antibody, Auto-antibodies to tropomyosin etc etc… the list goes on. But the fact remains that these are only detected in a certain percentage of patients ranging from ~20% all the way up to say roughly 70%. Equally a percentage of perfectly healthy normal people (~1-10%) can also test positive for these circulating auto-antibodies. So it remains, locked in this perpetual “investigational” type state. Inconclusive. Never the less, the fact that a larger portion of IBD patients test positive vs controls suggests they may (and should) play some role in the disease.
But does all that sound familiar in a way???? It’s the polar opposite of the the MAP controversy thing. You have a similar and ranging percentage of patients testing positive yet also having controls testing positive. Funny how that all goes.
So in both cases why do ~80% to ~20% of Inflammatory Bowel Disease patents test negative? Obviously this demonstrates that it’s perhaps not the whole story. Or perhaps even none of the story at all.
Over time (or more correctly study) some auto-antibodies/antibodies have been shown to cross-react/directly react respectively with bacteria and this in turn lead to the idea or thought that perhaps there is a case of Antigen (or Molecular) Mimicry or perhaps an abnormal response to normal bacteria going on. But again nothing has ever been conclusive.
The term autoimmunity means that natural unresponsiveness to self-antgens has been broken for some reason (known or unknown). This then leads, or more so directs immune reactions against one’s own tissues. So fine, this now allows the immune system to destroy self tissues. And this of course is not a good thing because in this case no resolution will EVER take place until the particular antigen/antibody/auto-antibody is eliminated from our body one way or another. This situation is simply not good.
When we’re younger however, T-cells are educated NOT to do the above (see last paragraph in this post in light of new evidence against this). Or at least this is what is supposed to happen. Sometimes this process does in fact go wrong. Essentially all proposed mechanisms of auto-immunity are thought to trace back to Th (Helper T Cells) as the primary mediator of auto-immunity.
Even so, any process can go wrong; be it T-cell, B-cells or Cellular Immune Responses and so on. If Inflammatory Bowel Disease is an auto-immune condition one would need to figure out just where in this whole mess of cr@p something has gone wrong. This is certainly not an easy task. Most likely why nothing is conclusive yet.
So there is a whole mess of things/processes that could go wrong and cause a misregulated immune response.
In regards to misregulation of the immune response one could look at B-cells specifically. Instead of making antibodies to foreign epitopes (another word for antigen) now they are making auto-antibodies to “modified” or “unmodified” structures on cell surface molecules. Sometimes drug or chemical induced modification of cell surface receptors can take place. So the left-overs from the therapy prior to being cleared, or even during therapy are modifying the cell surface structures in one way or another. Chemical alteration you could say. If there’s enough overlap between the modified and unmodified cell surface receptors then the antibodies are now going to be directed towards antigens on the host cell surface. In turn, the immune system is now going to mount an immune response directed at host tissues/cells. The question being what other environmental chemicals can we be exposed to in high enough levels or perhaps chronically that might do the same? No one knows. But there is speculation and suspicion.
Antigen mimicry would be another way for us to have a misregulated immune response - a region of the non-self protein or pathogen may resemble or even be exactly the same as a self-component. So polio virus, rabies virus, HIV and even MAP and yeast and many more have short bit’s of amino acids (5-8 amino acids in length) that have been identified to resemble a component in us. In some cases an antibody can be produced to target this short sequence of amino acids - and whamo, our immune response can be directed against self components. So this is an alternative being investigated. In some of us, have we previously been infected or are currently infected and is this Antigen Mimicry leading to the manifestation of an auto-immune condition?
And the questions continue with genetic susceptibility as in MHC2 molecules - so HLA types.
The whole thing get’s confusing at times but none the less there seem to be a lot of ways in which our bodies can target self components.
Regardless, at the end of the day there is still no complete consensus between researchers and GI’s etc. Only suspicion and opinion. Which sucks. I’m sure many of us find this unsettling that after so long, and so much research there is still no answer, very limited treatments and the possibility of surgery looming scares many. I’m sure many GI’s just say hey you have an auto-immune condition and you need to take immune suppressants simply to avoid having to tell their patients they are not really sure what is wrong with them and all they can do is try and treat them to the best of their ability with standardized treatment guidelines.
However “unsettling” the answer may be - the topic of auto-immunity is absolutely fascinating. Especially in light of the new study published a month or two ago that stated roughly an equal amount of auto-reactive T-cells are in fact produced and that something (an internal cellular process or molecule) is putting the breaks on them and preventing them from targeting self-tissues
medicalxpress.com/news/2015-05-adults-harbor-lots-risky-autoreactive.html I have no idea if this is in fact true, nor have I ever spoken to an immunologist or professor and anyone for that matter about
it - but it sure will be interesting to see where it goes down the road. Perhaps something like this has transpired in those of us with IBD…. Yet another theory that can be added to the pile.
Heck even some of the Crohn's Disease MAP researchers at this point feel UC might be a true auto-immune condition, but they are just as much at a loss to explain it as others.
It sure would be nice to see someone get to a definitive answer though. And I honestly don't think anyone cares overly deeply about
"what" that answer is - just an answer and a fix.
EDIT: And to be perfectly honest I actually do pay very, very close attention to the possible auto-immune aspect though I may not ever come across as if I do. I should perhaps exercise more caution as it does a disservice to all the work the has went into trying to understand these aspects. So it's disrespectful to the researchers, many who have probably spent oodles and oodles of hours trying to help us. But that's a two way or perhaps three or four way street in regards to other theories and laboratory efforts.
Post Edited (Canada Mark) : 6/19/2015 7:16:55 PM (GMT-6)