# Crohn's is not an autoimmune disorder



## Phil5813 (Oct 31, 2014)

Hello, my fellow Crohnies! I hope you're all doing well.

I've been perusing reddit quite a bit in the past month, and being that I'm in a flare (well, coming out of one now, thanks to Humira), I would keep an eye out for anything Crohn's-related. I never really saw much until tonight. I feel obliged to share this info with you all.

Reddit is host to many different kinds of people, and there are many subforums for virtually anything you can think of. There's a subforum called "Ask Me Anything" which is when someone answers other users' questions. Barack Obama, Buzz Aldrin, Bill Gates, and Neil deGrasse Tyson have answered questions, just to name a few.

So, on to the Crohn's. A user with a PhD in medical science who also has Crohn's recently posted this golden nugget of information:

"I don't have too much time. Therefore, a very simplified answer: it has been shown in the last ten years that Crohn's is not an autoimmune disease (which always seemed absurd) but rather the result of a barrier dysfunction. That means that the immune system in CD patients overreacts not because it is intrinsically broken but because it comes permanently into contact with bacteria when it shouldn't - because the intestinal barrier fails to keep the normal commensal bacteria away from it. Many genetic mutations associated with CD (NOD2, ATG16L1 etc.) have been linked to Paneth cell dysfunction: these cells reside at the bottom of the intestinal crypt and among other things secrete defensins which keep the crypts bacteria-free and regulate the microbiome.

In consequence, the problem with FT in this case is that microbial changes in Crohn's does not just happen by chance. Crohn's does not work like C. diff infection where we basically have an exogenously pertubated microbiome. Instead, the microbiome in CD is endogenously pertubated because the intestinal epithelium/Paneth cells is unable to create the right microenvironment for a healthy microbiome. Therefore, it is well possible that FT is correcting the microbiome in CD patients only transiently at most.

A good review about how everything is connected in CD is Knights et al. Gut 2013 ("Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome")."

He was responding to an inquiry about the effectiveness of fecal transplants, hence the reference to "FT."


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## JMC (Oct 31, 2014)

That is correct, the current research suggests it is not an autoimmune disease and most websites e.g. Wikipedia now reflect that fact.  Be wary of any doctor who still describes Crohn's as an autoimmune disease they are years out of date with their thinking.  I would also say that the immune system over reacting to commensal bacteria is a disputed theory. There is also very credible research which suggests Crohn's is caused by a bacterial pathogen with MAP and AIEC being the most likely candidates.


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## baistuff (Oct 31, 2014)

So if there is a fire in your house caused by a lightning strike are you not going to put out the fire in the house, because the source came from elsewhere? 

The immune response is there. It is an area that can be addressed to help control symptoms are prevent damage.  Sure, the "lightning strike" is likely bacterial and that needs to be addressed. But most IBD patients need the fire to be put out, and curbing the immune response (whether it's an overactive, response gone awry, or whatever else) is many IBDers is necessary today.


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## xeridea (Oct 31, 2014)

CCFA had a recent webcast where Dr. Corey A. Siegel, director of IBD Center at the Dartmouth-Hitchcock Med Ctr. said as much. In the Q&A someone referred to Crohn's as an autoimmune disease and Dr. Siegel said that CD is not an autoimmune disease but rather an immune dysfunction, with likely a bacterial cause. 

From reading hundreds of posts on this board, I get the sense that most of the more thoughtful folks agree that you have to pro-actively treat this disease and quell the underlying inflammation to prevent damage. Unfortunately not all treatments work for everybody and some of the treatment side-effects are nasty.

So we're all in quest for a cure or at least better treatment options.


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## JMC (Oct 31, 2014)

xeridea said:


> CCFA had a recent webcast where Dr. Corey A. Siegel, director of IBD Center at the Dartmouth-Hitchcock Med Ctr. said as much. In the Q&A someone referred to Crohn's as an autoimmune disease and Dr. Siegel said that CD is not an autoimmune disease but rather an immune dysfunction, with likely a bacterial cause.


Do you have a link to that?  I can only find webcasts from 2009.


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## Lisa (Oct 31, 2014)

JMC said:


> Do you have a link to that?  I can only find webcasts from 2009.


I haven't found the actual webcast yet - but I have a date - 



> Start Date: October 30, 2014
> Time: 5:00-6:15 PM
> Email Print + ShareExpert speaker Dr. Corey A. Siegel shares the latest information about Biologic Therapy. In this webinar you will:
> •Review the use of biologic therapy in Crohn’s and colitis
> ...


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## wildbill_52280 (Oct 31, 2014)

> Therefore, it is well possible that FT is correcting the microbiome in CD patients only transiently at most.


Its too soon to even know that and there is evidence which suggest otherwise. 

I vaguely recall the microbiome submits chemical messages to tell these cells to create antimicrobial defensins. If there is one concept that defines what is going on in IBD it is loss of colonization resistance against pathogens by lack of diversity of good bacteria. We accumulate pathogens like nobodys business and the diarrhea is another response to try to get rid of these pathogens. Even the disregulation of the inflammatory response is included in this definition, pathogens are attracted to chronic inflammation producing higher amount of nitrates which help bad bacteria to thrive. but really it would be stupid to oversimplify all the pathological processes that are going on, but that is the most general way of defining the disease. intestinal barrier disfunction, yea that's pretty important too. but the bacteria that line the intestine creates a barrier, and contributes to tight junction proteins, so to say it is a matter of barrier dysfunction is just saying the same thing as, the bacterial coat of armor is "messed up" ha.


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## xeridea (Oct 31, 2014)

JMC said:


> Do you have a link to that?  I can only find webcasts from 2009.


At the beginning of the call they said that a recording will be posted online next month.


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## xmdmom (Oct 31, 2014)

See if this link works for you 
https://www.webcaster4.com/Webcast/ListenPage?companyId=682&webcastId=5720
Only some browsers work. 
This page allowed me to listen to the 10/30 webinar today.


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## Phil5813 (Oct 31, 2014)

baistuff said:


> So if there is a fire in your house caused by a lightning strike are you not going to put out the fire in the house, because the source came from elsewhere?
> 
> The immune response is there. It is an area that can be addressed to help control symptoms are prevent damage.  Sure, the "lightning strike" is likely bacterial and that needs to be addressed. But most IBD patients need the fire to be put out, and curbing the immune response (whether it's an overactive, response gone awry, or whatever else) is many IBDers is necessary today.


You make a good point. But to go further, once the fire is out, wouldn't it be nice to take measures so that your house is never struck by lightning again? The biggest problem with tackling the lightning strike, however, is that..."firefighters" (a.k.a. the pharmas) will have a massive reduction in business. I worry that a cure will never really come out because of this. My GI told me that these studies are funded by pharmaceutical companies, but is it in the name of the common good, or in the name of better profit? I believe it's the latter.

This got kind of off-topic...


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## kiny (Oct 31, 2014)

It doesn't meet any of the requirements to be an autoimmune disease, there's no identifiable self-antigen in crohn's disease patients. The inflammation is patchy and isn't directed at tissue itself.  

UC is another question, because in UC the whole organ is inflamed, it's much more reasonable to argue that UC has autoimmunity, colon epithelial cells could be the self-antigen, which would mean there's autoimmunity, it would explain the non-specificity of the whole organ being inflamed in UC patients.

It's unreasonable for crohn's disease, it doesn't make any sense, it never has.

You don't even need the genetic precursors related to autophagy and bacterical clearance, all you need is to show that there's no consistently identifiable self-antigen in crohn's disease, it fails the first requirement to be an autoimmune disease.


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## kiny (Oct 31, 2014)

baistuff said:


> So if there is a fire in your house caused by a lightning strike are you not going to put out the fire in the house, because the source came from elsewhere?
> 
> The immune response is there. It is an area that can be addressed to help control symptoms are prevent damage.  Sure, the "lightning strike" is likely bacterial and that needs to be addressed. But most IBD patients need the fire to be put out, and curbing the immune response (whether it's an overactive, response gone awry, or whatever else) is many IBDers is necessary today.


I don't think anyone disputes that the inflammation needs to be controlled. But inflammation itself and the treatment with anti-inflammatories can not be used as an argument for autoimmunity.

People with infections get treated with anti-inflammatories too, imuran and corticosteroids have been used to treat infections, anti-inflammatories are used to prevent organ failure during infections, anti-inflammatories are used to prevent nerve damage during infections. None of these diseases have anything to do with autoimmunity, yet all of them are treated with medication, often overlapping with crohn's disease medication, since the priority is often stopping the destructive inflammation being caused by the infection, before the infection itself is treated.

It is important to recognise that crohn's disease is not an autoimmune disease, since crohn's disease should and can not be used as platform for pharma testing of treatments for autoimmune diseases.

UNLESS both patients and doctors recognise that croh's disease is not UC, that crohn's disease is not like an autoimmune disease, that  biologics outside of infliximab (and it's derivaties) used to treat autoimmune diseases have all failed to treat crohn's disease, there will never be better treatment for crohn's disease.

ONLY when crohn's disease gets the respect it deserves, a disease unlike any other, not caused by a self-antigen, that involves immune deficiencies related to bacterial handling, will we get treatment that truly helps and possibly cures us.

There is nothing more detrimental than using the term IBD to describe crohn's disease. It assumes UC and Crohn's disease overlap, should be treated similarly, it ignores the genetic differences, and it sets back progress for both diseases, since nothing could be further from the truth.


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## Lady Organic (Oct 31, 2014)

kiny said:


> There is nothing more detrimental than using the term IBD to describe crohn's disease. It assumes UC and Crohn's disease overlap, should be treated similarly, it ignores the genetic differences, and it sets back progress for both diseases, since nothing could be further from the truth.


what about indeterminate colitis? Im described as UC-LIKE Crohn's! I have shown different patterns of disease activity over 13 years, really looking and behaving like UC, but some very rare, small and occasional isolated healthy patches in recto-colon and one isolated episode in ileon and cacum...
There are so many different ways CD can express itself in different patients, in different organs, its even hard for me to accept lumping them all together and label all of them as CD.


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## my little penguin (Oct 31, 2014)

I agree - there are so many variations on presentation and then which med type will reduce symptoms - I think crohn's is just that an umbrella where a few variables are sometimes the same.
A lot of things need to change including the cause abd classification so treatments can be tailored better to the subtype .


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## rollinstone (Nov 1, 2014)

Hopefully once genetic testing gets more advanced they can give patients a more specified and effective treatment protocol. Sort of like what Dr. Forscythe does for his cancer patients, they do accurate genetic tests to show what will be most beneficial to each patient and go from there. Saying that, I definitely think crohns is an umbrella term with a variety of causes, I.e map or AIEC, the good news is its exciting times because there are things happening focusing on this, I.e qu biologics ssi and anti-map vaccine and the rhb trial, not to mention the huge focus on the microbiome. I think (well pray) "crohns" will absolutely cured in the near future. But yeah any doctor calling it an autoimmune disease need an update because it's not helpful for progress


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## JMC (Nov 1, 2014)

Lady Organic said:


> what about indeterminate colitis? Im described as UC-LIKE Crohn's! I have shown different patterns of disease activity over 13 years, really looking and behaving like UC, but some very rare, small and occasional isolated healthy patches in recto-colon and one isolated episode in ileon and cacum...


Without a definitive test for Crohn's disease, this is always going to be a potential issue.  I think if I was in your position, I would consider changing doctor.



Lady Organic said:


> There are so many different ways CD can express itself in different patients, in different organs, its even hard for me to accept lumping them all together and label all of them as CD.


That is why it is now being described as a syndrome by the more progressive thinkers in the field


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## Lady Organic (Nov 1, 2014)

JMC said:


> Without a definitive test for Crohn's disease, this is always going to be a potential issue.  I think if I was in your position, I would consider changing doctor.


why? I do get proper treatment for what is available now. for my condition in recto-colon, treatments available are the same whether the disease is UC, CD or indeterminate. My first GI was long term professor in GI specializing in IBD in my province. I was under his care for 10 years until he passed away and my case was always unclear to him. same with my new GI, although my new one put the term ''UC-like crohns'' since he's the one who discovered the ileon inflammation once.


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## JMC (Nov 2, 2014)

Lady Organic said:


> why?


Just my opinion, but given that UC and Crohn's are very different diseases, as explained by Kiny earlier in this thread, I would want a clear diagnosis as to which one I had as the treatment regimes should be different.


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## Phil5813 (Nov 3, 2014)

kiny said:


> UNLESS both patients and doctors recognise that croh's disease is not UC, that crohn's disease is not like an autoimmune disease, that  biologics outside of infliximab (and it's derivaties) used to treat autoimmune diseases have all failed to treat crohn's disease, there will never be better treatment for crohn's disease.


Would you count Humira as a derivative? It's working pretty well for me so far, though the pain is still there. Just curious about your opinion on it.


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## kiny (Nov 3, 2014)

Phil5813 said:


> Would you count Humira as a derivative? It's working pretty well for me so far, though the pain is still there. Just curious about your opinion on it.


Yes. Reason I said "Infliximab and derivatives" is because only the anti-TNF that work like infliximab do are effective.

There are anti-TNF like etanercept and a few others that are completely ineffective for crohn's disease, however, they are effective to treat a whole host of autoimmune diseases.

Showing again that crohn's disease, is very different from an autoimmune disease. Where autoimmune diseases have a whole host of biologics that work, crohn's disease does not.

In the last decade it has become more and more apparent that the inflammation is not a reaction to a self antigen, but bacterial handling is behind the inflammation in crohn's disease, which explains why medication that work for autoimmune diseases, doesn't translate to effective medication for crohn's disease. In fact in almost all cases, medication that can treat a whole host of autoimmune disease, is completely ineffective for crohn's disease. This is the reason why the most effective medication to treat crohn's disease, infliximab and it's derivatives, is over a decade old now and yet it has remained the medication with the highest remission rates for a decade.

I don't think this is something to be depressed about either, I think this is something that gives us a much higher chance for an eventual cure. An immune system that regards tissue as foreign, a self-antigen response, is something that is hugely complex and not something you would expect a cure for in the near fugure. However, when the antigen is pathogenic, like it probably is in crohn's disease, or if there is a loss of tolerance to intestinal bacteria, a path to a cure is possible.


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