Perhaps why some do and most dont get IBD

My UC started during a period of extreme stress and broad spectrum antibiotics being introduced at the same time. It's nice to see stress being added back into the picture. In the older days doctors believed that stress was a factor in IBD but over the last few years they have pretty much blown stress off in being involved. I think people are off track in believing that IBD is related to dysbiosis only. The immune system is out of whack and that's why many treatments target the weakening of the immune system. We're never going to get anywhere unless we go down the immune system path so I'm glad this seems to be pointing us in the right direction, in my opinion.

I looked back at some old blood tests, I don't remember having any discussion about IG levels so don't know why they did it (recently got copies of my medical records hence have these copies) but 3 years ago it looks like I had IGA, IGG and IGM tested, it is listed under "proteins"

For IGA ref range is .8 - 4.00 (g/l) and my reading was 2.3 - from what I remember I was not in flare at this time but was getting a lot of aches and pains in legs/feet

The IGM was actually high 0.5 - 2 g/l ref range and I tested at 4.13 - it was not discussed though with me and never re-tested

I had my serum IgA, IgG sublasses 1-4, IgE, IgM all tested. All were within normal range. Some were on the low ends of normal, i think the IgG ones, but normal nonetheless.

And here i'm with severe UC.

I don't know if serum blood tests will show the correct results,what we are talking about here is secretory intestinal

igA.

Tunnel: UC people are low,but not sure how they are testing this,it may say how but I am just not sure. May have missed it in all the papers.  At any rate from the above papers,there might be a good chance we are deficient in sIgA that coupled with barrier breach is enough to set off UC.

All this stuff is hard to tease out of zillions of papers on UC.  The familial aspect of crohns and leaky gut, points

me to see if in IBD discordant monozygotic twins there is any connection with IgA,but may not be able to find any data.  Also go back to the other igA thread, I have posted some more papers that explain more of what is going on with igA.

Like I said above I have been looking for a good reason why WT mice heal after DSS, and the question that we all ask. Why us and not everyone else,that has stress,has taken antibiotics or ate a crappy diet.

This provides one possible explanation.

Old Mike

Post Edited (Old Mike) : 9/1/2014 5:53:53 PM (GMT-6)

In a way the answer may be the same in everyone but the triggers may be different.

Totally forgot to mention earlier that it was suggested quite some time ago that although sIgA (secretory) is low, or seems to be low in some IBD patients - the reason suggested (and it makes a heck of a lot more sense now) is that all the sIgA is actually used up and stuck to the darn bacteria, whereas in controls it's not and free floating............

So when sampled for it's not picked up due to the methods used. This was an older hypothesis, but in light of the new sIgA study it makes a TON of sense.

Again pointing to the response to bacteria aspect - and that sometimes simple observations make a heck of a lot of sense.

Post Edited (Canada Mark) : 9/1/2014 9:54:12 PM (GMT-6)

Mark: Low sIgA might fit in with the problem of not enough specific amino acids which are used to make

immune complexes and muc2 during inflammation in UC. Threonine, proline, serine ,and cysteine,the body uses these to make the complexes at the expense of making muc2.  But it is my understanding that sigA is a dimer

of serum igA so you would think that serum igA would always be low during inflammation.  Both muc2 and igA are

glycoproteins.

Tunnel: We may also have anticolon antibodies.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1536205/pdf/clinexpimmunol00151-0173.pdf

but cant find much new work on them.

Old Mike

Hmmm. Maybe we're attacking both our colons and gut bacteria but treating the gut bacteria that the immune system is responding to could yield a great, consistent reduction of symptoms according to the IgA coating paper.

I actually have no idea though. When it starts getting into antibody talk, I kinda lose track of what is going on.

Here's an interesting paper I found on autoimmune factors, reactions to gut bacteria, and gut barrier function: www.wjgnet.com/1007-9327/full/v19/i43/7569.htm

It mentions in there that a previous infection could initiate sensitivity to commensal bacteria because the barrier function was significantly compromised. I had a bad infection for at least 3 weeks May 2013 in my colon...perhaps the round of antibiotics compromised my barrier and the reaction to gut bacteria is what is going on. But I don't know how many people with UC or CD now had prior infections in their intestinal tract.

I totally forgot about autoantibodies. I was getting so excited about the idea that the immune system was simply attacking bacteria that I didn't think about them.

EDIT: Another interesting paper. Molecular mimicry when it comes to the ANCA antibodies that we know are present in UC. It's saying that they could be reacting to bacteria...

www.ncbi.nlm.nih.gov/pubmed/15848155

Post Edited (Tunnelvisionary) : 9/2/2014 9:05:34 AM (GMT-6)

I agree with looking at autoimmune diseases in general Gary. I think progress in any area of AI research can eventually yield benefits to anyone facing an AI disease. That's not to say every single research project is extremely relevant to all AI diseases, but the general progress in figuring out how they work and finding better ways to stop them can be beneficial to all.

With how potentially effective probiotics, fecal transplants, and antibiotics are in some people with IBD, I do think that the mucus barrier and gut bacteria hold the key to finding way better therapeutic options for those of us with IBD. Gut bacteria can influence the immune system and some bacteria are known to have an effect on conditions like arthritis. With how complex that whole system is and the relationships with each other, I think it could be entirely plausible that UC is not a true autoimmune disease, but just a complicated immune-mediated disease. The recent IgA coating study did support the idea that bacteria greatly influence symptoms of colitis. ANCA antibodies could be marking other bacteria and not our own cells. Mucoprotective drugs seem to help a good amount without all the side effects according to preliminary results. I think there is a lot of good that can be done focusing on the mucus barrier/gut bacteria angle and it could be closely related to the root cause as it would influence the immune system. Certain types of bacteria might excite body beyond a certain threshold to initiate an autoimmune response, and if that's the case, altering the bacteria may increase the threshold to stop the autoimmune response. This suggests how dysbiosis may be a possible factor in the autoimmune response itself.

Even if it may not get at the true cause, perhaps therapy focused on maintaining the mucus barrier and killing off troublesome bacteria can yield great improvement in lots of people. Having another, way safer option with more reliable results would be a great thing to have as far as UC treatment goes.

The complexity and amount of things we don't know about the immune system and our gut bacteria yet make me reluctant to say UC is for sure a true autoimmune disease, but I could be wrong about that, and time will tell.

If that is the case, general autoimmune research seems to have taken a big step in a positive direction when researchers were able to reprogram mice' immune systems to stop the autoimmune response in established AI diseases without compromising the ability to fight infections or cancer. Hopefully the same process can be applied to humans.

What I can say for sure is that the disease is complex any way you look at it, and if it was easy to figure out, there would be a cure already. But I feel hopeful about the different directions research is taking.